Progestin Primed Ovarian Stimulation (PPOS) protocol yields lower euploidy rate in older patients undergoing IVF.

BACKGROUND: To explore if exogenous progestin required for progestin primed ovarian stimulation (PPOS) protocol compromises the euploidy rate of patients who underwent preimplantation genetic testing cycles when compared to those who received the conventional gonadotropin-releasing hormone (GnRH) antagonist protocol. METHODS: This retrospective cohort study analyzed 128 preimplantation genetic testing for aneuploidy (PGT-A) cycles performed from January 2018 to December 2021 in a single university hospital-affiliated fertility center. Infertile women aged 27 to 45 years old requiring PGT-A underwent either PPOS protocol or GnRH-antagonist protocol with in-vitro fertilization (IVF) or intracytoplasmic sperm injection (ICSI) for fertilization. Frozen embryo transfers were performed following each PGT-A cycle. Data regarding the two groups were analyzed using the Statistical Package for Social Sciences (SPSS) version 22.0 (SPSS Inc., Chicago, IL). RESULTS: Patients who underwent PPOS treatment had significantly reduced blastocyst formation rate and euploidy rate compared to those who received the GnRH antagonist protocol. Subgroup-analysis was performed by stratifying patients' age into elder and young subgroups (elder: ≥ 38-year-old, young: < 38-year-old). In the elder sub-population, the blastocyst formation rate of the PPOS group was significantly lower than that of the GnRH-antagonist group (45.8 ± 6.1% vs. 59.9 ± 3.8%, p = 0.036). Moreover, the euploidy rate of the PPOS group was only about 20% of that of  the GnRH-antagonist group (5.4% and 26.7%, p = 0.006). In contrast, no significant differences in blastocyst formation rate (63.5 ± 5.7% vs. 67.1 ± 3.2%, p = 0.45) or euploidy rate (30.1% vs. 38.5%, p = 0.221) were observed in the young sub-population. Secondary outcomes, which included implantation rate, biochemical pregnancy rate, clinical pregnancy rate, live birth rate, and miscarriage rate, were comparable between the two treatment groups, regardless of age. CONCLUSION: When compared to the conventional GnRH-antagonist approach, PPOS protocol could potentially reduce the euploidy rate in aging IVF patients. However, due to the retrospective nature of this study, the results are to be interpreted with caution. Before the PPOS protocol is widely implemented, further studies exploring its efficacy in larger populations are needed to define the optimal patient selection suitable for this method. TRIAL REGISTRATION: Human Investigation and Ethical Committee of Chang Gung Medical Foundation (202200194B0).

Oocyte-specific disruption of adrenomedullin 2 gene enhances ovarian follicle growth after superovulation.

Background: Adrenomedullin 2 (ADM2), adrenomedullin (ADM), and calcitonin gene-related peptides (α- and ß-CGRPs) signal through heterodimeric calcitonin receptor-like receptor/receptor activity-modifying protein 1, 2 and 3 (CLR/RAMP1, 2 and 3) complexes. These peptides are important regulators of neurotransmission, vasotone, cardiovascular development, and metabolic homeostasis. In rodents, ADM is essential for regulating embryo implantation, fetal-placental development, and hemodynamic adaptation during pregnancy. On the other hand, ADM2 was shown to affect vascular lumen enlargement, and cumulus cell-oocyte complex (COC) communication in rodent and bovine ovarian follicles. To investigate whether oocyte-derived ADM2 plays a physiological role in regulating ovarian folliculogenesis, we generated mice with oocyte-specific disruption of the Adm2 gene using a LoxP-flanked Adm2 transgene (Adm2 loxP/loxP) and crossed them with Zp3-Cre mice which carry a zona pellucida 3 (Zp3) promoter-Cre recombinase transgene. Results: While heterozygous Adm2 +/-/Zp3-Cre and homozygous Adm2 -/-/Zp3-Cre mice were fertile, Adm2 disruption in oocytes significantly increased the number of ovulated oocytes following a superovulation treatment. Oocyte-specific Adm2 disruption also significantly impaired the developmental capacity of fertilized eggs and decreased the size of the corpus luteum following superovulation, perhaps due to a reduction of ovarian cyclin D2-associated signaling. Conclusions: The disruption of intrafollicular ADM2 signaling leads to follicular dysfunction. These data suggested that oocyte-derived ADM2 plays a facilitative role in the regulation of hormonal response and follicle growth independent of the closely related ADM and CGRP peptides, albeit in a subtle manner.

Restoring tubal patency with laparoscopic tubocornual anastomosis.

OBJECTIVE: To assess the technical feasibility of laparoscopic tubocornual anastomosis (TCA) at restoring tubal patency in patients with proximal tubal occlusions. MATERIALS AND METHODS: A retrospective analysis of fourteen females with identified proximal tubal occlusions seeking to restore their tubal patency in a university-affiliated tertiary hospital between 2011 and 2018. Tubal patency within one year after the surgery was evaluated. RESULTS: The patients had a mean age of 34.0 ± 3.6 years old, median parity of 1 child, and mean BMI of 23.0 ± 5.2 kg/m2. Of the fourteen patients, two (14.3%) received bilateral TCA, eight (57.1%) received only unilateral TCA, and four (28.6%) received TCA on one side and tubal anastomosis on the other. The operative time was 126.4 ± 37.9min for unilateral procedure and 201.0 ± 1.4 min for bilateral anastomoses. Postoperative hysterosalpingogram (HSG) demonstrated a patency rate of 64.2% at the TCA sites. Two ectopic pregnancies were reported thereafter. CONCLUSION: This preliminary series demonstrates that laparoscopic TCA is technically feasible and provides promising results for patients with proximal tubal occlusions hoping to restore their tubal function in order to conceive naturally. A larger prospective series is mandatory to establish its significance and application in clinical practices. Notably, infertile patients without surgically correctable factors are not suitable for this procedure.