Luteal Phase Ovarian Stimulation versus Follicular Phase Ovarian Stimulation results in different Human Cumulus cell genes expression: A pilot study.

Background: Luteal-phase ovarian stimulation (LPOS) is an alternative in vitro fertilization (IVF) protocol. However, limited data showed the genes expression of cumulus cells (CCs) in LPOS. Therefore, this study aimed to investigate CC genes expression between LPOS and follicular-phase ovarian stimulation (FPOS) in poor ovarian responders (PORs) undergoing IVF cycles. Methods: This was a prospective non-randomized trial (ClinicalTrials.gov Identifier: NCT03238833). A total of 36 PORs who met the Bologna criteria and underwent IVF cycles were enrolled. Fifteen PORs were allocated to the LPOS group, and 21 PORs were allocated to the FPOS group. The levels of CC genes involved in inflammation (CXCL1, CXCL3, TNF, PTGES), oxidative phosphorylation (NDUFB7, NDUFA4L2, SLC25A27), apoptosis (DAPK3, BCL6B) and metabolism (PCK1, LDHC) were analyzed using real-time quantitative PCR and compared between the two groups. Results: The number of retrieved oocytes, metaphase II oocytes, fertilized oocytes, day-3 embryos and top-quality day-3 embryos, clinical pregnancy rates and live birth rates were similar between the two groups except for significantly high progesterone levels in the LPOS group. The mRNA expression levels of CXCL1 (0.51 vs 1.00, p < 0.001) and PTGES (0.30 vs 1.00, p < 0.01) were significantly lower in the LPOS group than in the FPOS group. The LPOS group had significantly lower mRNA expression of NDUFB7 (0.12 vs 1.00, p < 0.001) and NDUFA4L2 (0.33 vs 1.00, p < 0.01) than the FPOS group. DAPK3 (3.81 vs 1.00, p < 0.05) and BCL6B (2.59 vs 1.00, p < 0.01) mRNA expression was significantly higher in the LPOS group than in the FPOS group. Increased expression of PCK1 (3.13 vs. 1.00, p < 0.001) and decreased expression of LDHC (0.12 vs. 1.00, p < 0.001) were observed in the LPOS group compared to the FPOS group. Conclusions: Our data revealed different CC genes expression involving in inflammation, oxidative phosphorylation, apoptosis and metabolism between LPOS and FPOS in PORs. However, the results are non-conclusive; further large-scale randomized controlled trials are needed to validate the results.

Luteal phase stimulation versus follicular phase stimulation in poor ovarian responders: results of a randomized controlled trial.

BACKGROUND: In young women with poor ovarian response, luteal-phase ovarian stimulation (LPOS) is a potential method for collecting competent oocytes. The aim of this study was to assess the efficacy of LPOS compared with follicular phase ovarian stimulation (FPOS) in young women with poor ovarian response (POR). METHODS: This single-center, prospective, randomized pilot study compared LPOS and FPOS in women with POR fulfilling Bologna criteria who underwent in vitro fertilization at the Instituto Bernabeu. The primary outcome was the number of metaphase II (MII) oocytes obtained by follicular puncture. RESULTS: Sixty women were included in the study, with 27 women completing LPOS and 30 undergoing FPOS. There was no statistically significant difference in the number of MII oocytes obtained between the LPOS group and the FPOS group (2.1 ± 2.0 vs. 2.6 ± 2.2, p = 0.31). Length of stimulation was also similar in both groups (8.35 ± 2.8 vs. 8.15 ± 4.1 days, p = 0.69). Similarly, there was no significant difference in the follicle-stimulating hormone total dose, number of cumulus-oocyte complexes, survival rate, fertilization rate, or cancellation rate between groups. A significantly higher Ovarian Sensitivity Index was observed in the LPOS group versus the FPOS group (0.96 vs. 0.57, p = 0.037). CONCLUSION: LPOS was comparable with FPOS in terms of efficacy and may improve ovarian responsiveness in young women with POR. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02625532; EudraCT identifier: 2015-003856-31.

Late Follicular Phase Ovarian Stimulation Without Exogenous Pituitary Modulators.

Introduction: A gonadotropin-releasing hormone antagonist is the most common modulator used to prevent the premature luteinizing hormone (LH) surge when ovarian stimulation was initiated in the late follicular phase. We aimed in this study to evaluate the feasibility of performing ovarian stimulation in the late follicular phase without the use of exogenous pituitary modulators. Methods: Data were retrospectively collected from 404 normo-ovulatory patients who underwent their first in vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatment in our department. One hundred sixteen subjects in the study group received ovarian stimulation when a dominant follicular diameter of ≥ 10 mm was confirmed by transvaginal ultrasonography after menstrual cycle day 6, which entailed a daily injection of gonadotropin until the trigger day, while 288 subjects in the control group received ovarian stimulation in the early follicular phase under a progesterone protocol. The primary outcome was the number of mature oocytes. Results: There was no statistical difference in the number of mature oocytes between the two groups (9.67 ± 5.33 in the study group vs. 9.38 ± 5.15 in the control group, P = 0.693). No secondary LH surges in the study group and no premature LH surges in the control group were found during ovarian stimulation. The good-quality embryo rate per oocyte retrieved showed no significant difference between the two groups (35.22 vs. 35.91%, P = 0.665). The clinical pregnancy rate per transfer was 54.55% in the study group and 56.48% in the control group (P = 0.718), and the implantation rate was similar between the two groups (36.94 vs. 37.77%, P = 0.829). Conclusions: Our study revealed that late follicular phase ovarian stimulation could be performed without an exogenous pituitary modulator.

Luteal Phase Ovarian Stimulation May Improve Oocyte Retrieval and Oocyte Quality in Poor Ovarian Responders Undergoing In Vitro Fertilization: Preliminary Results from a Single-Center Prospective Pilot Study.

INTRODUCTION: Luteal phase ovarian stimulation (LPOS) has been proven a feasible protocol for infertile patients. High progesterone level in the luteal phase could physiologically inhibit premature luteinizing hormone surge, from which poor ovarian responders (PORs) could obtain benefits. Therefore, we aimed to compare clinical outcomes between LPOS and follicular phase ovarian stimulation (FPOS) protocol in PORs undergoing in vitro fertilization (IVF). METHODS: This prospective pilot study was performed at one tertiary center from January 2016 to October 2017. A total of 60 PORs who met Bologna criteria and undergoing IVF were enrolled. Thirty PORs were allocated to the LPOS group and 30 PORs were allocated to the FPOS group. Basic characteristics, cycle characteristics, and pregnancy outcomes were compared between the two groups. RESULTS: The length of stimulation was significantly longer in the LPOS group than in the FPOS group. The numbers of retrieved oocytes, metaphase II oocytes, fertilized oocytes, and day-3 embryos were significantly higher in the LPOS group than in the FPOS group. Conversely, we could not find any significant difference for clinical pregnancy rate, ongoing pregnancy rate, abortion rate, and cancellation rate. The multivariate analysis showed that only LPOS (p = 0.007) was significantly associated the possibility to retrieve three or more oocytes, whereas basal follicle-stimulating hormone (FSH) < 8 IU/l (p = 0.103) and antral follicle count (AFC) ≥ 3 (p = 0.143) did not significantly affect this event. CONCLUSION: LPOS allows improved oocyte retrieval and oocyte quality in PORs with respect to FPOS, despite comparable pregnancy outcomes. LPOS may be considered a feasible option for oocytes accumulation in PORs. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT03238833.