الفهرس 
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Abstract
A major challenge in the field of assisted reproductive technologies is managing premature ovulation. It is common practice to limit pituitary activity and avoid the premature rise of luteinizing hormone (LH) by using gonadotropin-releasing hormone (GnRH) analogs, which can be either an agonist or an antagonist. After forty years of research, we know these drugs work and are safe to use.
More flexible regimens have been proposed using vitrification as of late. The widespread use of progestin in conjunction with GnRH analogue to delay ovulation is one such example. Patients enduring ovarian stimulation during freeze-all in vitro fertilization treatments now have a realistic alternative with the progestin-primed ovarian stimulation (PPOS) regimen.
But PPOS has not yet demonstrated its effectiveness in clinical situations. In particular, epidemiological studies have not yet determined whether ovarian stimulation, in conjunction with the extra dose of progestin, influences oocyte quality and, by extension, embryo competence.
Clinical trials have shown that PPOS is just as effective as the GnRH antagonist protocol, the short protocol in the freeze-all scenario, and the ultra-long GnRH agonist protocol in terms of egg yields and pregnancy outcomes.
New evidence from retrospective studies suggests that higher progesterone levels may reduce oocyte and embryo quality. Another prospective clinical trial indicated that early miscarriage was equally common in PPOS as in GnRH agonist or antagonist regimens, but the sample size was too small to draw any firm conclusions. There were also very few articles that dealt with the topic of full-term pregnancy monitoring.
Concerning the possibility of miscarriage following a confirmed positive serum HCG test, there is a lack of data. To evaluate the embryo’s viability for in vitro fertilization, it is important to look at the percentage of pregnancies that fail following confirmed positive blood HCG tests.
The main aim of this study was to compare the outcome of vitrified embryos originating from Progestin Primed Ovarian Stimulation vs. outcome of vitrified embryos originating from GnRH analogue protocols especially as regard: Pregnancy outcome and neonatal birth weights.
This study included all case files In Nile IVF Centre within January 2022 till December 2022 divided into 2 groups: group A: Vitrified embryos originated from PPOS protocol. group B: Vitrified embryos originated from conventional protocols using GnRH analogue group.
The main results of the study revealed that:
• one treated with GnRH Analogue and the other with PPOS, showed no significant differences in maternal age (p=0.675), paternal age (p=0.195), or BMI (p=0.731). This indicates a balanced distribution of demographic variables between the groups, enhancing the comparability of our study cohorts. (Table 1)
• Regarding infertility duration, the distribution among groups demonstrated that 68.2% of the GnRH Analogue group experienced a duration of 1-3 years, compared to 72.0% in the PPOS group (p=0.570). Gravidity and the number of miscarriages exhibited similar patterns, with no significant variations between the groups (p=0.924 and p=0.518, respectively).
• Analysis of induced abortions, parity, and previous IVF attempts also revealed no significant discrepancies between the GnRH Analogue and PPOS groups (p=0.409, p=0.347, and p=0.776, respectively). The distribution of infertility indications, including tubal factors, male factors, unexplained causes, anovulatory conditions, endometriosis, and mixed causes, displayed no statistically significant differences between the groups (p=0.7677).
• Regarding Oocyte Yields, no significant differences were observed between the two groups across different yield categories (1-5, 6-15, and 16-35), with p-values ranging from 0.926 to 0.855.
• Endometrium Preparation methods, however, showed a significant difference (p=0.044*). Notably, the PPOS group had a higher percentage of patients undergoing natural cycle preparation (21.5%) compared to the GnRH Analogue group (35.2%). Endometrium Thickness demonstrated no significant disparities between groups (p=0.854), with the majority in both groups having an endometrial thickness >8 mm.
• Examining Embryo Stage, a significant difference (p=0.037*) was observed. The GnRH Analogue group had a higher percentage of patients with embryos in the cleavage stage (75.0%), while the PPOS group had a higher proportion with blastocysts (87.1%), showed a significant difference (p=0.037*). Embryos Transferred displayed no significant differences between groups (p=0.801), indicating a balanced distribution of the number of embryos transferred during ART cycles.
• Finally, the Basic FSH value exhibited no statistically significant difference between the GnRH Analogue and PPOS groups (p=0.385).
• The overall pregnancy loss rates were found to be 18.2% in the GnRH Analogue group and 20.4% in the PPOS group, with an odds ratio (OR) of 1.155 and a 95% confidence interval (CI) of 0.551-2.422. The p-value of 0.702 indicates no statistically significant disparity in pregnancy loss rates between the two treatment groups.
• In the assessment of pregnancy outcomes and neonatal variables within our study cohorts treated with GnRH Analogue (N=72) and PPOS (N=74), no significant differences were observed between the two groups across various parameters. The live birth rate was 79.2% in the GnRH Analogue group and 79.7% in the PPOS group, with an odds ratio of 0.966 (95% CI: 0.433-2.156) and a p-value of 0.933.
• Gestational weeks at delivery did not show significant variations between the groups (p=0.787), with a majority of deliveries occurring after 37 weeks in both cohorts. Similarly, the mode of delivery (vaginal or cesarean section), the number of neonates (single or twins), and the sex of neonates demonstrated no statistically significant differences between the GnRH Analogue and PPOS groups.
• Birth weight, represented by mean ± SD and median (IQR), also exhibited no significant differences between the two groups (p=0.928). Furthermore, the percentages of low birthweight (<2500 g) and high birthweight (>4000 g) infants were comparable between the GnRH Analogue and PPOS groups, with odds ratios close to 1 and non-significant p-values.
• Neonatal events and congenital anomalies were infrequent in both groups, and no significant differences were observed in their occurrences (p=0.700 and p=0.551, respectively). These findings suggest that the incidence of adverse neonatal outcomes did not significantly differ between individuals treated with GnRH Analogue and PPOS.
Conclusion
Results from this retrospective cohort analysis showed that compared to cycles employing GnRH analogue protocols, FET cycles using embryos from the PPOS procedure had comparable rates of pregnancy loss throughout the whole pregnancy and birth weight of babies. These results provide to a clearer picture of the PPOS protocol’s safety profile in COS.
The research suggests that the use of external progestins during ovarian stimulation does not have a negative impact on the quality of eggs or the ability of embryos to develop in IVF/ICSI cycles.
Additional assessment and future investigations should prioritize the examination of the prolonged safety of infants born from PPOS methods.