A delayed ovulation of progestin-primed ovarian stimulation (PPOS) by downregulating the LHCGR/PGR pathway

Xie, Yunying; Guo, Wei; Shen, Xi; Yu, Weidong; Kuang, Yanping; Chen, Qiuju; Long, Hui; Lyu, Qifeng; Wang, Li

doi:10.1016/j.isci.2023.107357

Cited by 5 publications

(2 citation statements)

References 57 publications

(84 reference statements)

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“…Matrix metalloproteinase with thrombospondin type 1 motifs-1 (ADAMTS-1) in the ovaries is localized in the cumulus-oocyte complex and carries out the degradation of large-sized aggregating proteoglycans, including versican, which is necessary for the reorganization of the extracellular matrix and the normal course of folliculogenesis and ovulation [85,86]. The expression and functional activity of ADAMTS-1 in cumulus cells are closely related to the ability of the oocyte to fertilize [35], and a decrease in the expression of this metalloproteinase is associated with impaired maturation and quality of oocytes in women with polycystic ovary syndrome [86][87][88][89]. Expression of the gene encoding ADAMTS-1 begins several hours after administration of LH or hCG, as a response to gonadotropin-induced increases in the level of proinflammatory factors, and was elevated until ovulation, after which it decreased during the CL formation [90,91].…”

Section: Discussionmentioning

confidence: 99%

Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats

Derkach,

Lebedev,

Morina

et al. 2023

IJMS

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Gonadotropins, including human chorionic gonadotropin (hCG), are used to induce ovulation, but they have a number of side effects, including ovarian hyperstimulation syndrome (OHSS). A possible alternative is allosteric luteinizing hormone (LH)/hCG receptor agonists, including the compound TP4/2 we developed, which remains active when administered orally. The aim was to study the effectiveness of TP4/2 (orally, 40 mg/kg) as an ovulation inducer in FSH-stimulated immature female rats, compared with hCG (s.c., 15 IU/rat). TP4/2 stimulated progesterone production and corpus luteum formation; time-dependently increased the ovarian expression of steroidogenic genes (Star, Cyp11a1, Cyp17a1) and genes involved in ovulation regulation (Adamts-1, Cox-2, Egr-1, Mt-1); and increased the content of metalloproteinase ADAMTS-1 in the ovaries. These effects were similar to those of hCG, although in some cases they were less pronounced. TP4/2, in contrast to hCG, maintained normal LH levels and increased the ovarian expression of the LH/hCG receptor gene, indicating preservation of ovarian sensitivity to LH, and did not cause a sustained increase in expression of vascular endothelial growth factor-A involved in OHSS. Thus, TP4/2 is an effective ovulation inducer that, unlike hCG, has a lower risk of OHSS and ovarian LH resistance due to its moderate stimulating effect on steroidogenesis.

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Section: Discussionmentioning

confidence: 99%

Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats

Derkach,

Lebedev,

Morina

et al. 2023

IJMS

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“…Xie et al observed how administration of PPOS in a mouse model was associated with suppressed LH levels prior to the trigger and a decrease in progesterone synthesis afterwards, leading to a delay in ovulation that seemed to be due to a downregulation of the LHCGRÀPGR pathway. These data suggest that the trigger to oocyte retrieval interval (TORI) in PPOS cycles should be longer than the usual 36 h adhered to in conventional protocols with GnRH analogues [15]. However, it should be noted that these findings have not been reproduced in humans at the level of steroidogenesis and the study did not include a control group that received GnRH antagonists [2…”

Section: Trigger and Interval To Oocyte Retrievalmentioning

confidence: 99%

Progestin-primed ovarian stimulation

Giles,

Cruz,

Garcia-Velasco

2024

Current Opinion in Obstetrics &Amp; Gynecology

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Purpose of review The use of progestins as pituitary suppressors has increased progressively, along with more detailed indications for their use, thereby consolidating an alternative approach to the personalization of ovarian stimulation. Recent findings Based on the ability of progesterone to inhibit ovulation, progestins have been used in ovarian stimulation (OS) follicular protocols to prevent a luteinizing hormone surge in patients undergoing in vitro fertilization (IVF), as an alternative to gonadotropin-releasing hormone (GnRH) analogue administration. This review explores the different types of progestogen protocols and their efficacy depending on the type of population or reproductive procedure in which they are administered and in comparison with that of GnRH analogues. Their effect on oocytes and embryos and their safety and cost-effectiveness are also analyzed. Summary Progestins have proven their effectiveness as a gonadotropin adjuvant in terms of ovarian response, reproductive outcome, and safety. In addition, they offer the convenience of oral administration and a lower cost than GnRH analogues. Whereas oocytes or embryos should be vitrified as it displaces the receptive period with the consequent asynchrony between embryo and endometrium. The evidence endorses progestins as a more friendly approach to OS, especially when frozen-thawed embryo transfer is planned.

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Should the trigger to oocyte retrieval interval be different in progestin-primed ovarian stimulation cycles?

Ata,

Cakar,

Türkgeldi

et al. 2024

Reproductive BioMedicine Online

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A delayed ovulation of progestin-primed ovarian stimulation (PPOS) by downregulating the LHCGR/PGR pathway

Cited by 5 publications

References 57 publications

Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats

Comparison of Steroidogenic and Ovulation-Inducing Effects of Orthosteric and Allosteric Agonists of Luteinizing Hormone/Chorionic Gonadotropin Receptor in Immature Female Rats

Progestin-primed ovarian stimulation

Should the trigger to oocyte retrieval interval be different in progestin-primed ovarian stimulation cycles?

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