Immunohistochemical localization of Placental Growth Factor (PlGF) in human endometrium. Proliferative phase endometrium showing diffuse weak immunostaining for PlGF in glandular epithelium (GE) and leukocytes (Δ)(A). More intense staining was seen in the early-secretory (B), mid-secretory (C) and late-secretory (D) phases. Immunoreactive staining was localized in basal luminal 'vesicles' of the GE in the early-secretory phase (B) these immunoreactive vesicles were apically located in the mid-secretory (D) and late secretory (F) phase, as indicated by arrowheads. Immunoreactive protein was also detected in blood vessels and decidualising stroma surrounding the spiral arterioles (C & E; indicated by arrows). (Endometrial biopsies; n = 5–7 samples/phase of the cycle). No staining was observed in the negative control (isotype matched IgG). Scale bar on A and E = 100 μm, B and C = 200μm, D and F = 50μm.  

Immunohistochemical localization of Placental Growth Factor (PlGF) in human endometrium. Proliferative phase endometrium showing diffuse weak immunostaining for PlGF in glandular epithelium (GE) and leukocytes (Δ)(A). More intense staining was seen in the early-secretory (B), mid-secretory (C) and late-secretory (D) phases. Immunoreactive staining was localized in basal luminal 'vesicles' of the GE in the early-secretory phase (B) these immunoreactive vesicles were apically located in the mid-secretory (D) and late secretory (F) phase, as indicated by arrowheads. Immunoreactive protein was also detected in blood vessels and decidualising stroma surrounding the spiral arterioles (C & E; indicated by arrows). (Endometrial biopsies; n = 5–7 samples/phase of the cycle). No staining was observed in the negative control (isotype matched IgG). Scale bar on A and E = 100 μm, B and C = 200μm, D and F = 50μm.  

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Embryo implantation requires synchronized dialogue between the receptive endometrium and activated blastocyst via locally produced soluble mediators. During the mid-secretory (MS) phase of the menstrual cycle, increased glandular secretion into the uterine lumen provides important mediators that modulate the endometrium and support the conceptus du...

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Background: The opening and closing of the implantation window is important for successful pregnancy in eutherians. The recent study demonstrated that the window of uterine receptivity was prepared by the sole action of progesterone in mice, but the mechanism to close the window remained to be elucidated. Methods: The pregnant mice were ovariect...

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... leading to tissue damage and early pregnancy losses 14 . It was further shown that PlGF modifies cellular motility and adhesion with important roles in early pregnancy 15 . Low levels of PlGF are associated with PE and used as a clinical diagnostic marker for PE prediction 13,18 , but it remains uncertain whether dysregulated low PlGF level is a cause or consequence of PE progression. ...
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Cell stiffness is regulated by dynamic interaction between ras-related C3 botulinum toxin substrate 1 (Rac1) and p21 protein-activated kinase 1 (PAK1) proteins, besides other biochemical and molecular regulators. In this study, we investigated how the Placental Growth Factor (PlGF) changes endometrial mechanics by modifying the actin cytoskeleton at the maternal interface. We explored the global effects of PlGF in endometrial stromal cells (EnSCs) using the concerted approach of proteomics, atomic force microscopy (AFM), and electrical impedance spectroscopy (EIS). Proteomic analysis shows PlGF upregulated RhoGTPases activating proteins and extracellular matrix organization-associated proteins in EnSCs. Rac1 and PAK1 transcript levels, activity, and actin polymerization were significantly increased with PlGF treatment. AFM further revealed an increase in cell stiffness with PlGF treatment. The additive effect of PlGF on actin polymerization was suppressed with siRNA-mediated inhibition of Rac1, PAK1, and WAVE2. Interestingly, the increase in cell stiffness by PlGF treatment was pharmacologically reversed with pravastatin, resulting in improved trophoblast cell invasion. Taken together, aberrant PlGF levels in the endometrium can contribute to an altered pre-pregnancy maternal microenvironment and offer a unifying explanation for the pathological changes observed in conditions such as pre-eclampsia (PE).
... The well-established factors of angiogenic activity are vascular endothelial growth factor (VEGF) family members, including placental growth factor (PlGF), and their receptors (VEGFRs), basic fibroblast growth factor (bFGF, also known as FGF2) and its receptors (FGFRs), as well as angiopoietins 1 and 2 (ANG-1, ANG-2) and their receptor (TIE2) (for review, see Hyder and Stancel 1999;Lockwood et al. 2004). Previous studies have confirmed the expression of all above-mentioned angiogenesis-related factors and their receptors in uterine tissues of various species (Wordinger et al. 1992;Edwards et al. 2011;Lash et al. 2012;Binder et al. 2016;Hayashi et al. 2019). Besides endothelial cells, VEGFs and their receptors have also been found in endometrial luminal epithelial cells (LEc) and glandular epithelial cells (GEc). ...
... VEGF-A has also been found in stromal cells (STc) of the bovine endometrium (Hayashi et al. 2019). Placental growth factor was immunolocalised in human GEc and blood vessels (Binder et al. 2016). Interestingly, in mice, bFGF was found to be strongly expressed in the basal lamina associated with LEc, whereas diffuse expression was observed also in the extracellular matrix of endometrial stroma (Wordinger et al. 1992). ...
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Context The appropriate course of angiogenesis in the endometrium is crucial for pregnancy establishment and maintenance. Very little is known about the factors linking vessel formation and immune system functioning. Aims We hypothesised that chemerin, an adipokine known for its involvement in the regulation of energy balance and immunological functions, may act as a potent regulator of endometrial angiogenesis during early pregnancy in pigs. Methods Porcine endometrial tissue explants were obtained from pregnant pigs on days 10–11, 12–13, 15–16 and 27–28, and on days 10–12 of the oestrous cycle. The explants were in vitro cultured for 24 h in the presence of chemerin (100, 200 ng/mL) or in medium alone (control). We evaluated the in vitro effect of chemerin on the secretion of vascular endothelial growth factors A–D (VEGF-A–D), placental growth factor (PlGF), basic fibroblast growth factor (bFGF) and angiopoietin 1 and 2 (ANG-1, ANG-2) with the ELISA method. The protein abundance of angiogenesis-related factor receptors, VEGF receptors 1–3 (VEGFR1–3), FGF receptors 1 and 2 (FGFR1–2) and ANG receptor (TIE2) was evaluated with the Western blot (WB) method. We also analysed the influence of chemerin on the phosphorylation of AMPK using WB. Key results We found that in the studied endometrial samples, chemerin up-regulated the secretion of VEGF-A, VEGF-B and PlGF, and protein expression of VEGFR3. The adipokine caused a decrease in VEGF-C, VEGF-D and ANG-1 release. Chemerin effect on bFGF and ANG-2 secretion, and protein content of VEGFR1, VEGFR2, FGFR1, FGFR2 and TIE2 were dependent on the stage of pregnancy. Chemerin was found to down-regulate AMPK phosphorylation. Conclusions The obtained in vitro results suggest that chemerin could be an important factor in the early pregnant uterus by its influence on angiogenic factors’ secretion and signalling. Implications The obtained results on the role of chemerin in the process of endometrial angiogenesis may, in the long term perspective, contribute to the elaboration of more effective methods of modifying reproductive processes and maintaining energy homeostasis in farm animals.
... Влияние PlGF на васкулогенез проявляется опосредованно через стимуляцию мобилизации мезенхимальных предшественников эндотелиальных клеток, которые участвуют в васкулогенезе. PlGF вовлечен в имплантацию бластоцисты, рост, дифференцировку и инвазию трофобласта [12,26]. PlGF синтезируется преимущественно клетками цитотрофобласта, но также был обнаружен в слизистой оболочке матки: в стромальных децидуальных клетках, железистом и люминальном эпителии матки, предецидуальных стромальных клетках в секреторной фазе маточного цикла. ...
... PlGF синтезируется преимущественно клетками цитотрофобласта, но также был обнаружен в слизистой оболочке матки: в стромальных децидуальных клетках, железистом и люминальном эпителии матки, предецидуальных стромальных клетках в секреторной фазе маточного цикла. Также он детектируется в сердце, легких, коже (кератиноциты, эндотелий сосудов дермы) [12,26]. Стимулами для повышения экспрессии PlGF служит секреция факторов роста, гормонов и провоспалительных цитокинов. ...
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The normal development and functioning of the placenta can be due to the proper regulation of the vasculogenesis and angiogenesis processes. Factors that regulate vasculogenesis and angiogenesis are the VEGF family and their receptors (VEGFR-1, VEGFR-2 and VEGFR-3). The disbalance of these factors leads to aberrant development of placental vessels which results in pathological disorders of placentation and can be associated with pregnancy complications such as preeclampsia, gestational hypertension, preterm birth, fetal growth retardation, acute fetal hypoxia. Mild placental angiogenesis disorders may not have obvious clinical manifestations, such as those that develop in preeclampsia and fetal growth retardation. However, due to the influence of trigger factors in childbirth, inadequate angiogenesis can lead to decompensation of placental circulation which is clinically manifested as acute fetal hypoxia. This review presents a brief characteristic and description of the main functions of the factors regulating angiogenesis, namely the VEGF family (VEGF-B, VEGF-C, VEGF-D, VEGF-E, VEGF-F, PlGF) and their receptors (VEGFR-1, VEGFR-2 and VEGFR-3), their role in physiological or pathological vasculogenesis and angiogenesis of the placenta. The changes in angiogenic factors in the maternal blood in normal pregnancy/childbirth and in pathology, as well as in different methods of delivery, are presented. The effect of labor and induction of labor on changes in angiogenic factors is shown and the pathophysiological mechanisms underlying these changes are described. This review presents a modern perspective on the possibilities of predicting complications of pregnancy and childbirth based on monitoring of these factors. Conclusion: The level of angiogenic factors in the maternal peripheral blood correlates with the morphofunctional state of the placenta. The profile of angiogenic factors is likely to reflect a particular clinical picture of placental insufficiency including a latent form that does not manifest itself during pregnancy but leads to fetal hypoxia during childbirth.
... In the endometrial tissue, under rising levels of progesterone, there is an increase in glandular secretion which is crucial for the synthesis and transport of mediators into the endometrial cavity, providing support and modulating the embryonic implantation [2]. The implantation process involves apical bonding and adhesion of the trophoblast cells to the endometrial epithelium. ...
... PIGF is predominantly located in the luminal/glandular epithelial cells of the endometrium throughout the menstrual cycle (fertile and infertile group), as well as in the cells surrounding the maternal spiral arteries during the secretory phase. Its location varies according to the phase of the cycle: during the early secretory phase it is located in basal layer of the epithelial cells and in the late stage it is located in apical region, being released into uterine secretions [2]. It is also detectable in maternal serum, which allows preeclampsia to be signaled when there is an early and marked decrease in its serum levels [2]. ...
... Its location varies according to the phase of the cycle: during the early secretory phase it is located in basal layer of the epithelial cells and in the late stage it is located in apical region, being released into uterine secretions [2]. It is also detectable in maternal serum, which allows preeclampsia to be signaled when there is an early and marked decrease in its serum levels [2]. ...
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Background Embryo implantation is a complex biological process which requires synchronized dialogue between the receptive endometrium and the blastocyst. The endometrium, however, is only receptive to embryo implantation for a very short period. Recurrent implantation failure (RIF) is a major challenge in assisted reproductive techniques mainly due to impaired receptivity, but there is still a need for a reliable and valid clinical test to assess endometrial receptiveness, especially at embryo transfer time. The aim of this review is to investigate what is currently known about the contribution of endometrial fluid (EF) to endometrial receptivity by identifying its potential biomarkers. Methods This study involved an extensive search of the electronic databases PubMed and Cochrane, covering the period from 2011 to 2022. A combination of Medical Subject Headings with the terms ‘endometrial fluid’ and ‘embryo implantation’ was used. Results Several different proteins presented in the endometrial cavity fluid have been described but the most consistent as potential biomarkers were Proprotein Convertase 6 (PC6), Vascular Endothelial Growth Factor (VEGF), PIGF (Placental growth factor), β3 integrin, Colony Stimulating Factor-3 (CSF-3), Leukaemia inhibitory factor (LIF), glycodelin and extracellular vesicles (EVs). Conclusions Strong indicators support the use of uterine fluid collection as a non-invasive tool for receptivity assessment. Therefore, it could improve outcomes of assisted reproductive techniques.
... Olaya et al (10) had concluded that umbilical cord abnormalities were associated with maternal gestational hypertension, with these umbilical cord abnormalities being ultimately associated with fetal and neonatal consequences (10). Pre-eclampsia has been connected to malformed VEGF family placental proteins, which have also been mentioned as crucial for embryo growth and implantation (11). ...
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Introduction: The coiling of the umbilical vessels develops by about 28 days post-conception and is present in about 95% of foetuses by around nine weeks of conception. Umbilical coiling (UC) is associated with many maternal and fetal outcomes. The present study attempts to assess any associations between medical disorders of pregnancy with umbilical cord coiling. Methodology: This cross-sectional study was conducted in the A total of 300 obstetric mothers were included in the study. Coiling of the umbilical cord numbers and pattern and umbilical coiling index was assessed at the time of delivery. Medical disorders such as diabetes mellitus, hypertension and thyroid disorders during pregnancy were evaluated at the time of delivery. Data was entered and analysed with Epi info software. Results: Gestational diabetes mellitus was seen in hyper-coiled and normocoiled, but not also in hypocoiled UC. Hypothyroidism with GDM was seen only in hypocoiled UC. A significant association was seen with selected endocrinal medical problems with umbilical cord coiling (P value <0.05). The most common blood pressure-related disorder identified in the present study is eclampsia (66.66%). Gestational hypertension was seen only in hypocoiled UC coiling. Conclusion: The most common endocrine disorder associated with umbilical cord coiling was gestational diabetes in hyper coiled and normocoiled UC. Hypocoiling and normocoiling have been found in medical disorders of pregnancy. Multicentric studies are required to identify the relationship between endocrine and blood pressure-related disorders and umbilical coiling.
... Placental growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, is a pivotal regulator for the onset and maintenance of early pregnancy and secreted by DSCs, trophoblast cells, and dNK cells (15)(16)(17). Up to the present, Fms-like-tyrosine-kinase receptor 1 (FLT-1) is the only known signaling receptor for PlGF in humans and expresses on endothelial cells, osteoclasts, smooth muscle cells, fibroblasts, angiogenesis-competent myeloid progenitors, tumour cells, T cells, and monocyte/macrophage lineage cells (18)(19)(20). PlGF/FLT-1 is best known for its involvement in placental angiogenesis and maternal spiral arteries remodeling via regulating physiological activities of endothelial cells during early pregnancy (18,21,22). ...
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Introduction Dysregulated macrophage polarization (excessive M1-like or limited M2-like macrophages) in the early decidua contributes to allogeneic fetal rejection and thus early spontaneous abortion. However, the modulators of M1/M2 balance at the early maternal-fetal interface remain mostly unknown. Methods First-trimester decidual tissues were collected from normal pregnant women undergoing elective pregnancy terminations and patients with spontaneous abortion. We measured the expression of placental growth factor (PlGF) and Fms-like-tyrosine-kinase receptor 1 (FLT-1), and characterized the profiles of macrophages in decidua. Notably, we investigated the effect of recombinant human PlGF (rhPlGF) on decidual macrophages (dMφs) from normal pregnancy and revealed the underlying mechanisms both in vitro and in vivo. Results The downregulated expression of PlGF/ FLT-1 may result in spontaneous abortion by inducing the M1-like deviation of macrophages in human early decidua. Moreover, the CBA/J×DBA/2 abortion-prone mice displayed a lower FLT-1 expression in uterine macrophages than did CBA/J×BALB/c control pregnant mice. In in vitro models, rhPlGF treatment was found to drive the M2-like polarization of dMφs via the STAT3/CEBPB signaling pathway. These findings were further supported by a higher embryo resorption rate and uterine macrophage dysfunction in Pgf knockout mice, in addition to the reduced STAT3 transcription and C/EBPβ expression in uterine macrophages. Discussion PlGF plays a key role in early pregnancy maintenance by skewing dMφs toward an M2-like phenotype via the FLT-1-STAT3-C/EBPβ signaling pathway. Excitingly, our results highlight a rationale that PlGF is a promising target to prevent early spontaneous abortion.
... Interestingly, bevacizumab and ranibizumab only bind to VEGF, whereas aflibercept also binds to the placental growth factor (PlGF). PlGF may play a role in embryo development and implantation and in fetoplacental circulation [49]. Finally, corticosteroids were used as a reference group since they are widely used in pregnant women, especially systemic corticosteroids. ...
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This nationwide population-based cohort study aimed to describe the use of intravitreal injections (IVTs) of anti-vascular endothelial growth factor (anti-VEGF) agents and corticosteroids in pregnant women in France and to report on the incidence of obstetric and neonatal complications. All pregnant women in France who received any anti-VEGF or corticosteroid IVT during pregnancy or in the month preceding pregnancy from 1 January 2009 to 31 December 2018 were identified in the national medico-administrative databases. Between 2009 and 2018, there were 5,672,921 IVTs performed in France. Among these IVTs, 228 anti-VEGF or corticosteroid IVTs were administered to 139 women during their pregnancy or in the month preceding their pregnancy. Spontaneous abortion or the medical termination of pregnancy occurred in 10 women (16.1%) who received anti-VEGF agents and in one (3.1%) of the women who received corticosteroids (p = 0.09). This is the first national cohort study of pregnant women treated with anti-VEGF or corticosteroid IVTs. We found a high incidence of obstetric complications in pregnant women treated with anti-VEGF or corticosteroid IVTs but could not demonstrate a statistically significant association between the intravitreal agents and these complications. These agents should continue to be used with great caution in pregnant women.
... The placental growth factor (PlGF) is an angiogenic growth factor that belongs to the vascular endothelial growth factor (VEGF) family, which contains VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and VEGF-E, that is known for its role in regulating vasculogenesis and angiogenesis [8]. In addition, recent research has revealed an important role for PlGF in regulating placentation, implantation [9][10][11][12][13], ovarian angiogenesis [14], and ovulation [15]. Besides, imbalance in PlGF levels has been linked to several pregnancy complications like preeclampsia, giving birth of small for gestational age, preterm birth, and stillbirth [16][17][18][19]. ...
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Background Gonadotropin-releasing hormone (GnRH) analogues are used to prevent premature luteinizing hormone (LH) surge during In-Vitro Fertilization. However, the follicular fluid levels of the Placental growth factor (FF PlGF), the novel angiogenic factor, differ significantly between GnRH-agonist and GnRH-antagonist protocols. Thus, we compared the IVF/ICSI outcomes and their correlations with FF PlGF levels in polycystic ovary syndrome (PCOS) and normo-ovulatory women during different hyperstimulation protocols. Methods This case-control study is a re-analysis of two prospective trials that were conducted on women who were referred to Orient Hospital, Damascus, Syria, from December 2019 to August 2021. A total of 75 PCOS-women (PCOS-Agonist, n = 53; PCOS-Antagonist, n = 22) and 83 normo-ovulatory women (Control-Agonist, n = 50; Control-Antagonist, n = 33) were included. Follicular fluid samples were collected on retrieval day. Results Although PCOS-women were stimulated using lower gonadotropin doses, the Ovarian-sensitivity-indexes were higher in PCOS-groups (PCOS-Agonist vs Control-Agonist; P-value <0.001), (PCOS-Antagonist vs Control-Antagonist; P-value = 0.042). However, FF PlGF levels, maturation rate, fertilization rate, and oocytes morphology were comparable between PCOS and controls independently of the protocol used. Interestingly, FF PlGF levels were positively correlated with Ovarian-sensitivity-indexes in the PCOS-Antagonist, Control-Agonist, and Control-Anta groups, but not in the PCOS-Agonist group. Nevertheless, FF PlGF levels were comparable between pregnant and non-pregnant women in all studied groups. Conclusions Although PCOS exaggerates ovarian response to stimulation irrespective of the protocol used, it does not have a detrimental impact on oocytes morphology or competence. Moreover, FF PlGF levels could be a marker of the ovarian response other than a predictor of pregnancy achievement.
... Placental growth factor (PLGF) was another gene that may be associated with reproductive function, most notably with embryo implantation (52,53). PLGF was a member of the vascular endothelial growth factor family of proangiogenic factors regulated angiogenesis and microvessel density (MVD) (54,55). ...
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The hypothalamic–pituitary–adrenal (HPA) axis plays an important role in the growth and development of mammals. Recently, lncRNA transcripts have emerged as an area of importance in sheep photoperiod and seasonal estrus studies. This research aims to identify lncRNA and mRNA that are differentially expressed in the sheep adrenal gland in long (LP) or short (SP) photoperiods using transcriptome sequencing and bioinformatics analysis based on the OVX + E2 (Bilateral ovariectomy and estradiol-implanted) model. We found significant differences in the expression of lncRNAs in LP42 (where LP is for 42 days) vs. SP-LP42 (where SP is for 42 days followed by LP for 42 days) (n = 304), SP42 (where SP is for 42 days) vs. SP-LP42 (n = 1,110) and SP42 vs. LP42 (n = 928). Cluster analysis and enrichment analysis identified SP42 vs. LP42 as a comparable group of interest and found the following candidate genes related to reproductive phenotype: FGF16, PLGF, CDKN1A, SEMA7A, EDG1, CACNA1C and ADCY5. FGF16 (Up-regulated lncRNA MSTRG.242136 and MSTRG.236582) is the only up-regulated gene that is closely related to oocyte maturation. However, EDG1 (Down-regulated lncRNA MSTRG.43609) and CACNA1C may be related to precocious puberty in sheep. PLGF (Down-regulated lncRNA MSTRG.146618 and MSTRG.247208) and CDKN1A (Up-regulated lncRNA MSTRG.203610 and MSTRG.129663) are involved in the growth and differentiation of placental and retinal vessels, and SEMA7A (Up-regulated lncRNA MSTRG.250579) is essential for the development of gonadotropin-releasing hormone (GnRH) neurons. These results identify novel candidate genes that may regulate sheep seasonality and may lead to new methods for the management of sheep reproduction. This study provides a basis for further explanation of the basic molecular mechanism of the adrenal gland, but also provides a new idea for a comprehensive understanding of seasonal estrus characteristics in Sunite sheep.
... The placental growth factor (PlGF) is an angiogenic growth factor that belongs to the vascular endothelial growth factor (VEGF) family, which contains VEGF-A (also known as VEGF), VEGF-B, VEGF-C, VEGF-D, and VEGF-E, that is known for its role in regulating vasculogenesis and angiogenesis [8]. In addition, recent research has revealed an important role for PlGF in regulating placentation, implantation [9][10][11][12][13], ovarian angiogenesis [14], and ovulation [15]. Besides, imbalance in PlGF levels has been linked to several pregnancy complications like preeclampsia, giving birth of small for gestational age, preterm birth, and stillbirth [16][17][18][19]. ...
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Background Anti-Müllerian hormone (AMH) is a glycoprotein that plays an important role in the regulation of ovarian folliculogenesis. However, the data link between its follicular fluid levels (FF AMH) and the IVF/ICSI outcomes in polycystic ovary syndrome (PCOS) women are limited, contradicted, and mainly obtained from Long-GnRH agonist cycles. Thus, we conducted this study to compare the correlations between the FF AMH levels and the IVF/ICSI outcomes in PCOS women during different controlled hyperstimulation protocols. Methods The current study is a re-analysis of our previous work. The data were adopted from a prospective trial that was conducted on women who were referred to the Assisted Reproductive Unit of Orient Hospital, Damascus, Syrian Arab Republic, from December 2019 to August 2021. A total of 75 PCOS women (Rotterdam criteria) (GnRH agonist group, PCOS-A, n = 53; GnRH antagonist group, PCOS-Anta, n = 22) were included. Follicular fluid samples were collected on the retrieval day, and the FF AMH levels were measured using ELISA Kits. In addition, the embryological and clinical IVF/ICSI outcomes were detected. Spearman rank correlation coefficients were computed to assess the correlations among the studied parameters. The area under the receiver operating characteristic (ROC) curve (AUC) was used to evaluate the accuracy of FF AMH levels in predicting pregnancy rates. Results The patients’ baseline characteristics were comparable between the PCOSA and the PCOSAnta groups. FF AMH levels were negatively correlated with the total FSH dose, the number of retrieved, MII, MI, germinal vesicle, immature, and fertilized oocytes, and with the number of obtained embryos in the PCOSA group, but not in the PCOSAnta one. Nevertheless, there were not any correlations between FF AMH levels and the rates of oocyte maturation or fertilization, or with the highquality embryo rate, embryos cleavage rate or implantation rate in any of the studied groups. In addition, no significant differences were noted in FF AMH levels between pregnant and non-pregnant women in any of the studied groups, which also was confirmed by the Receiver Operating Characteristic (ROC) Curve analysis. Discussion Since the FF AMH levels do not correlate with the maturation rate, fertilization rate, or embryos cleavage rate, the negative correlations in the PCOSA group arise from the negative impacts of the FF AMH on the number of retrieved oocytes. During the long agonist protocol, since PCOS follicles have good follicular angiogenesis, the number of retrieved oocytes would mostly depend on the negative effects of the FF AMH on folliculogenesis. However, during the GnRH antagonist protocol, the limited angiogenesis acts together with the high levels of FF AMH to reduce the number of retrieved oocytes. Conclusions High FF AMH negatively affects ovarian folliculogenesis during both; the long GnRH agonist protocol and the flexible GnRH antagonist one. However, the different patterns of follicular angiogenesis during the two protocols would affect the dependency of the oocytes' yield on the follicular fluid levels of AMH. Study registration The data were adopted from a prospective clinical trial that was registered on the clinicaltrials.gov site by registration numbers NCT04727671.