The effect of intrauterine hCG injection before embryo transfer on pregnancy rate in frozen embryo transfer cycles

Jahanshahi, Mehrdad; Aleyasin, Ashraf; Aghahosseini, Marzieh; Najafian, Alireza; Nashtaei, Maryam Shabani; Hosseinimousa, Sedigheh

doi:10.1016/j.amsu.2022.104091

Cited by 3 publications

(4 citation statements)

References 20 publications

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“…EV-based strategies have been explored to improve fertility treatment candidates such as hCG [153][154][155][156], which have immunomodulatory and endometrial receptivity-enhancing effects. Indeed, uterine fluid EVs (UF-EVs), when actively loaded with hCG via sonication, prolonged hCG release and increased in vitro attachment rates at higher levels compared to native UF-EVs co-supplemented with hCG.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, NVs significantly increased (∼ 20%) the attachment rate of hTSC spheroids co‐cultured with confluent monolayers of the HEC1A endometrial epithelial cell line to model the epithelial phase of implantation in vitro. The endometrium receives signals from the implanting blastocyst, which heavily influences endometrial receptivity (e.g., embryonic hCG [153–156]) and blastocyst‐endometrial interactions (adhesome) [57]. We show that NVs, derived from the blastocyst trophectoderm, evoke similar responses in the endometrium to modulate its receptivity and adhesive capacity [57, 109, 157, 158].…”

Section: Discussionmentioning

confidence: 99%

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Rapid generation of functional nanovesicles from human trophectodermal cells for embryo attachment and outgrowth

Poh,

Rai,

Pangestu

et al. 2023

Proteomics

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Extracellular vesicles (EVs) are important mediators of embryo attachment and outgrowth critical for successful implantation. While EVs have garnered immense interest in their therapeutic potential in assisted reproductive technology by improving implantation success, their large‐scale generation remains a major challenge. Here, we report a rapid and scalable production of nanovesicles (NVs) directly from human trophectoderm cells (hTSCs) via serial mechanical extrusion of cells; these NVs can be generated in approximately 6 h with a 20‐fold higher yield than EVs isolated from culture medium of the same number of cells. NVs display similar biophysical traits (morphologically intact, spherical, 90–130 nm) to EVs, and are laden with hallmark players of implantation that include cell‐matrix adhesion and extracellular matrix organisation proteins (ITGA2/V, ITGB1, MFGE8) and antioxidative regulators (PRDX1, SOD2). Functionally, NVs are readily taken up by low‐receptive endometrial HEC1A cells and reprogram their proteome towards a receptive phenotype that support hTSC spheroid attachment. Moreover, a single dose treatment with NVs significantly enhanced adhesion and spreading of mouse embryo trophoblast on fibronectin matrix. Thus, we demonstrate the functional potential of NVs in enhancing embryo implantation and highlight their rapid and scalable generation, amenable to clinical utility.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Rapid generation of functional nanovesicles from human trophectodermal cells for embryo attachment and outgrowth

Poh,

Rai,

Pangestu

et al. 2023

Proteomics

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“…Proteomic [244][245][246] and transcriptomic [247,248] analyses of the cyclic, human endometrium have identified molecular markers of receptivity; recapitulating this receptivity signature in the endometrium prior to ET has thus been a focus for fertility treatments. Embryo-secreted hCG induces endometrial receptivity [249,250] in non-human primates; its intrauterine delivery to prime the endometrium towards an implantative state is thus a promising fertility treatment [251,252] (reviewed [253,254]) and has been explored in clinical trials (NCT01786252 [255], NCT01030393 [256]). Recently, Hajipour et al, engineered human UF-EVs loaded with the known embryonic signal hCG as an intrauterine supplement to increase endometrial receptivity.…”

Section: Engineered/modified Evsmentioning

confidence: 99%

Omics insights into extracellular vesicles in embryo implantation and their therapeutic utility

et al. 2023

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Implantation success relies on intricate interplay between the developing embryo and the maternal endometrium. Extracellular vesicles (EVs) represent an important player of this intercellular signalling through delivery of functional cargo (proteins and RNAs) that reprogram the target cells protein and RNA landscape. Functionally, the signalling reciprocity of endometrial and embryo EVs regulates the site of implantation, preimplantation embryo development and hatching, antioxidative activity, embryo attachment, trophoblast invasion, arterial remodelling, and immune tolerance. Omics technologies including mass spectrometry have been instrumental in dissecting EV cargo that regulate these processes as well as molecular changes in embryo and endometrium to facilitate implantation. This has also led to discovery of potential cargo in EVs in human uterine fluid (UF) and embryo spent media (ESM) of diagnostic and therapeutic value in implantation success, fertility, and pregnancy outcome. This review discusses the contribution of EVs in functional hallmarks of embryo implantation, and how the integration of various omics technologies is enabling design of EV‐based diagnostic and therapeutic platforms in reproductive medicine.

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“…Moving further, H-hCG could be administered during implantation and early placental formation to stimulate trophoblast invasion and reduce pregnancy failure and adverse outcomes due to placental dysfunction, including FGR and maybe preeclampsia. The concept of using H-hCG as a therapeutic method is not ground breaking, as “regular” hCG administration is already used in some IVF protocols to increase success rate, but H-hCG may prove to be more effective in promoting successful implantation [ 63 , 64 , 65 ]. Large-scale production of H-hCG as a commercially available drug is still a matter to be resolved, as there are important steps and procedures to be accomplished.…”

Section: Future Directionsmentioning

confidence: 99%

Hyperglycosylated-hCG: Its Role in Trophoblast Invasion and Intrauterine Growth Restriction

Herghelegiu

Veduță

Stefan

et al. 2023

Cells

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Human chorionic gonadotropin (hCG) is produced by the placenta and its roles have been studied for over a century, being the first known pregnancy-related protein. Although its main role is to stimulate the production of progesterone by corpus luteal cells, hCG does not represent just one biologically active molecule, but a group of at least five variants, produced by different cells and each with different functions. The hyperglycosylated variant of hCG (H-hCG) plays a key role in trophoblast invasion, placental development and fetal growth. During trophoblast invasion, H-hCG promotes extravillous cytotrophoblast cells to infiltrate the decidua, and also to colonize and remodel the spiral arteries in to low resistance, larger-diameter vessels. As fetal growth is heavily reliant on nutrient availability, impaired trophoblast invasion and remodeling of the uterine arteries, leads to a defective perfusion of the placenta and fetal growth restriction. Understanding the function of H-hCG in the evolution of the placenta might unveil new ways to manage and treat fetal growth restriction.

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The effect of intrauterine hCG injection before embryo transfer on pregnancy rate in frozen embryo transfer cycles

Cited by 3 publications

References 20 publications

Rapid generation of functional nanovesicles from human trophectodermal cells for embryo attachment and outgrowth

Rapid generation of functional nanovesicles from human trophectodermal cells for embryo attachment and outgrowth

Omics insights into extracellular vesicles in embryo implantation and their therapeutic utility

Hyperglycosylated-hCG: Its Role in Trophoblast Invasion and Intrauterine Growth Restriction

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