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Journal of Assisted Reproduction and... Oct 2018
Topics: Corpus Luteum; Female; Humans; Luteinization; Ovulation; Progesterone
PubMed: 30218419
DOI: 10.1007/s10815-018-1312-4 -
Journal of Assisted Reproduction and... Oct 2018Premature luteinization (PL) affects 12.3-46.7% of fresh in vitro fertilization cycles, and there is accumulating evidence confirming its negative effect on success... (Review)
Review
PURPOSE
Premature luteinization (PL) affects 12.3-46.7% of fresh in vitro fertilization cycles, and there is accumulating evidence confirming its negative effect on success rates. However, despite its clinical significance, PL is poorly understood and defined. This narrative review aims to provide a fresh look at the phenomenon of PL by summarizing the existing evidence and re-evaluating fundamental issues.
METHODS
A thorough electronic search was conducted covering the period from 1978 until January 2018 in PubMed, Embase, and Medline databases, and references of relevant studies were cross-checked. Meeting proceedings of the European Society of Human Reproduction and Embryology and the American Society for Reproductive Medicine were also hand searched.
RESULTS
In the curious case of PL, one should go back to the beginning and re-consider every step of the way. The pathogenesis, definition, measurement methods, clinical implications, and management strategies are discussed in detail, highlighting controversies and offering "food for thought" for future directions.
CONCLUSIONS
Authors need to speak the same language when studying PL in order to facilitate comparisons. The terminology, progesterone cut-off, measurement methods and days of measurement should be standardized and globally accepted; otherwise, there can be no scientific dialog. Future research should focus on specific patient profiles that may require a tailored approach. Progesterone measurements throughout the follicular phase possibly depict the progesterone exposure better than an isolated measurement on the day of hCG. Adequately powered randomized controlled trials should confirm which the best prevention and management plan of PL is, before introducing any strategy into clinical practice.
Topics: Chorionic Gonadotropin; Female; Fertilization in Vitro; Gonadotropin-Releasing Hormone; Humans; Luteinization; Ovulation Induction; Pregnancy; Pregnancy Rate; Premature Birth; Progesterone
PubMed: 30051348
DOI: 10.1007/s10815-018-1264-8 -
Journal of Assisted Reproduction and... Nov 2019The impact of the prematurely elevated serum progesterone on the late follicular phase, commonly known as premature luteinization (PL), is a matter of continuing debate.... (Review)
Review
The impact of the prematurely elevated serum progesterone on the late follicular phase, commonly known as premature luteinization (PL), is a matter of continuing debate. Available evidence supports that serum progesterone ≥ 1.5 ng/ml on the day of ovulation triggering could reduce the pregnancy potential in fresh in vitro fertilization (IVF) cycles by jeopardizing endometrial receptivity. Causes of PL during ovarian stimulation are unclear. Recent studies point toward the daily follicle-stimulating hormone dosage, duration of controlled ovarian stimulation, number of oocytes retrieved, and peak estradiol level as factors affecting the incidence of PL. Emerging data show additional influence on embryo quality. The prevention of PL has been challenging. The key elements in preventing PL include individualization of ovarian stimulation according to patient's ovarian reserve, proper ovulation trigger timing, and use of medications such as corticosteroids and metformin. Embryo cryopreservation with deferred embryo transfer is the established strategy to overcome PL, yet it is an extra burden to the IVF laboratory and increased cost for patients. Herein, we review the up-to-date knowledge of this frequent IVF problem including causes, proposed diagnostic criteria, and its impact on endometrial receptivity, embryo quality, and pregnancy outcomes. The preventive measures and rescue strategies are also discussed.
Topics: Female; Fertilization in Vitro; Humans; Luteinization; Ovary; Ovulation; Ovulation Induction; Pregnancy; Pregnancy Outcome; Reproductive Techniques, Assisted
PubMed: 31650455
DOI: 10.1007/s10815-019-01598-4 -
Folia Medica Dec 2020A collision tumor represents a coexistence of two adjacent but histologically distinct tumors without histologic admixture in an organ. Serous tumors of the ovary are... (Review)
Review
A collision tumor represents a coexistence of two adjacent but histologically distinct tumors without histologic admixture in an organ. Serous tumors of the ovary are the most common forms of epithelial tumors, and cavernous hemangiomas are rare in the ovary. Howev-er, a collision between them is an extremely rare pathology. Here the author presents a report of a 74-year-old woman whose ultrasound examines establishes rounded left ovary formation with hypo- and hyperdense sections. Paraclinical: CA125 within normal range. Serum levels free testosterone 3.79 nmol/l (normal 0.49-2.64 nmol/l for women). The histology showed benign serous cystadenoma and vascular lesions composed of capillary and cavernous vessels amongst luteinized stromal cells. The luteinized cells were positive for inhibin A. The endothelial cells were negative for estrogen and progesterone receptor. A search was conducted in the Medline database via PubMed using the terms: 'hemangioma', 'ovary', 'collision', 'serous cystadenoma', no more than 70 articles for ovarian hemangiomas appeared, and no articles for a collision between serous cystadenoma and mixed hemangioma with stromal luteinization in the ovary. From the reference, this is the first reported case of collision between serous cystadenoma and mixed cavernous-capillary hemangioma with stromal luteinization in the ovary. This rare case of collision between tumors in the ovary sheds light on possible tumor pathology in the woman's reproductive system, which must be considered by gynaecologists and pathologists.
Topics: Aged; Cystadenoma, Serous; Female; Hemangioma, Capillary; Hemangioma, Cavernous; Humans; Luteinization; Ovarian Neoplasms; Ovary; Rare Diseases; Stromal Cells; Ultrasonography
PubMed: 33415926
DOI: 10.3897/folmed.62.e51551 -
Frontiers in Bioscience : a Journal and... Jan 2007In recent years, significant progress was made, particularly through the use of the macaque monkey, in identifying three types of local factors that are induced by the... (Review)
Review
In recent years, significant progress was made, particularly through the use of the macaque monkey, in identifying three types of local factors that are induced by the midcycle LH surge and play a critical role in ovulation and/or luteinization of the primate follicle. The ovulatory gonadotropin surge increases prostaglandin (PTG, typically abbreviated PG) levels in follicles prior to rupture; although considerable attention has focused on LH stimulation of the "inducible" form of PG G/H synthase (PTGS2), other aspects of PG synthesis (notably a phospholipase A2, cPLA2, and a PGE synthase, PTGES) and metabolism (15-hydroxy PG dehydrogenase, HPGD) also appear LH-regulated and may control the timing of the PG rise in the ovulatory follicle. Local (intrafollicular) ablation and replacement of PGs suggests that PGE2 is essential for release of the oocyte; but not necessarily for follicle rupture, and not for luteinization. Novel PGE-regulated genes are being identified in macaque granulosa cells, including adipose differentiation-related protein (ADFP). Similar types of studies indicate that the rise in progesterone (P) synthesis, as well as the induction of the genomic P receptor in granulosa cells, is essential for both ovulation and luteinization of the primate follicle. Limited data suggest that P action controls cell cycle activity (via cyclin B1 and cyclin-dependent kinase inhibitor p27), cholesterol uptake and utilization (e.g., low density lipoprotein or LDL receptor), proteases and their inhibitors (matrix metalloproteinase or MMP1; tissue inhibitor of MMP or TIMP1) and cell health in the granulosa cell layer. Finally, members of two classes of angiogenic factors, originally proposed as important for embryonic and pathologic (tumorigenic) vasculogenesis, appear induced in the granulosa layer of the preovulatory follicle, i.e., vascular endothelial growth factor (VEGF) and angiopoietin (ANGPT). Local injection of antagonists to VEGF (soluble VEGF receptor) and ANGPT (the natural antagonist ANGPT2) into the preovulatory follicle suppressed ovulation and luteinization in monkeys, possibly by disrupting the structure-function of existing vessels or preventing angiogenesis in the avascular granulosa layer. Further studies using high-throughput genomic and proteomic analysis, particularly on specific cell types (e.g., granulosa, theca and microvascular cells) and distinct follicular regions (apex, base and cumulus-oocyte complex) of the dominant follicle in natural menstrual cycles, are needed. Such information is essential to advance our understanding of the cascade of events leading to ovulation and luteinization of the primate follicle, to unravel the causes of ovary-based infertility and to consider novel ovary-selective approaches to contraception.
Topics: Angiogenic Proteins; Animals; Female; Luteinization; Macaca; Ovarian Follicle; Ovulation; Progesterone; Prostaglandins
PubMed: 17127300
DOI: 10.2741/2065 -
Gynecological Endocrinology : the... Nov 2021Cancer therapy has priority over fertility preservation. The time available for fertility preservation in patients with cancer is often very limited and depends on the... (Review)
Review
Fertility preservation immediately after therapeutic abortion results in multiple normal follicular growth with the absence of mature oocytes due to early luteinization: a case report and literature review.
Cancer therapy has priority over fertility preservation. The time available for fertility preservation in patients with cancer is often very limited and depends on the condition of the underlying disease. This case report presents the results of two rounds of controlled ovarian stimulations (COSs) performed after an induced abortion. The patient had mixed phenotype acute leukemia diagnosed during early pregnancy and underwent a surgical abortion, followed by ovarian stimulation using urinary follicle-stimulating hormone (uFSH) and gonadotropin-releasing hormone (GnRH) agonists. Oocyte retrieval was subsequently performed for oocyte cryopreservation. Despite good hormonal and ultrasonic follicular growth, no oocytes were obtained. During a second COS performed at a low human chorionic gonadotropin (hCG) level (less than 100 IU/L), several mature oocytes were obtained, suggesting that higher hCG levels during COS induce the absence of mature oocytes during normal follicular growth. It is recommended to start COS post-abortion after confirming a low hCG level while considering the timing of cancer treatment.
Topics: Abortion, Induced; Female; Fertility Preservation; Humans; Luteinization; Oocyte Retrieval; Ovulation Induction; Pregnancy; Young Adult
PubMed: 34304673
DOI: 10.1080/09513590.2021.1950135 -
Differentiation; Research in Biological... 2023In the present study, granulosa cells (GCs) from domestic cats and Persian leopard were cultured and characterized from selected days. The culture period was divided...
In the present study, granulosa cells (GCs) from domestic cats and Persian leopard were cultured and characterized from selected days. The culture period was divided into two phases: maintenance, which lasted for 7 days, and luteinization, which followed for up to 11 days. Luteinization was performed on ultra-low attachment plates, supporting the formation of spheroids in a medium supplemented with insulin, forskolin, and luteinizing hormone (LH). GCs of domestic cat produced estradiol (E2) and progesterone (P4) during the maintenance phase. The gene expressions of some proteins involved in steroidogenesis were stable (STAR, HSD3B1) or decreased over time (CYP11A1, HSD17B1, CYP17A1, and CYP19A1), which was similar to the expressions of gonatropin receptors (LHCGR and FSHR). During the luteinization phase, P4 concentration significantly increased (P < 0.05), and E2, in contrast to the proliferation phase, was below detection range. The expression of genes of proteins involved in steroidogenesis (STAR, CYP11A1, HSD3B1, HSD17B1, CYP17A1, and CYP19A1) and of gonadotropin receptors (LHCGR and FSHR) significantly increased during the luteinization period, but some expressions exhibited a decrease at the end of the phase (LHCGR, FSHR, HSD17B1, CYP19A1). The morphology of the luteinized GCs of domestic cat resembled large luteal cells and had numerous vacuole-like structures. Also, the GCs of Persian leopard underwent luteinization, shown by increasing P4 production and HSD3B1 expression. This study confirms that GCs from felids can be luteinized in a 3D spheroid system which can be a basis for further studies on luteal cell function of felids. Additionally, we could show that the domestic cat can serve as a model species for establishing cell culture methods which can be transferred to other felids.
Topics: Female; Cats; Animals; Cholesterol Side-Chain Cleavage Enzyme; Granulosa Cells; Luteinization; Multienzyme Complexes; Panthera; Cells, Cultured
PubMed: 37079952
DOI: 10.1016/j.diff.2023.03.002 -
Science Advances Mar 2022Anti-Müllerian hormone (AMH) is produced by growing ovarian follicles and provides a diagnostic measure of reproductive reserve in women; however, the impact of AMH on...
Anti-Müllerian hormone (AMH) is produced by growing ovarian follicles and provides a diagnostic measure of reproductive reserve in women; however, the impact of AMH on folliculogenesis is poorly understood. We cotransplanted human ovarian cortex with control or AMH-expressing endothelial cells in immunocompromised mice and recovered antral follicles for purification and downstream single-cell RNA sequencing of granulosa and theca/stroma cell fractions. A total of 38 antral follicles were observed (19 control and 19 AMH) at long-term intervals (>10 weeks). In the context of exogenous AMH, follicles exhibited a decreased ratio of primordial to growing follicles and antral follicles of increased diameter. Transcriptomic analysis and immunolabeling revealed a marked increase in factors typically noted at more advanced stages of follicle maturation, with granulosa and theca/stroma cells also displaying molecular hallmarks of luteinization. These results suggest that superphysiologic AMH alone may contribute to ovulatory dysfunction by accelerating maturation and/or luteinization of antral-stage follicles.
Topics: Animals; Anti-Mullerian Hormone; Endothelial Cells; Female; Heterografts; Humans; Luteinization; Mice; Ovarian Follicle
PubMed: 35263130
DOI: 10.1126/sciadv.abi7315 -
Human Reproduction (Oxford, England) Apr 2023Do cortisol/glucocorticoid receptors play an active role in the human ovary during ovulation and early luteinization?
STUDY QUESTION
Do cortisol/glucocorticoid receptors play an active role in the human ovary during ovulation and early luteinization?
SUMMARY ANSWER
The ovulatory hCG stimulation-induced glucocorticoid receptor signaling plays a crucial role in regulating steroidogenesis and ovulatory cascade in human periovulatory follicles.
WHAT IS KNOWN ALREADY
Previous studies reported an increase in cortisol levels in the human follicular fluid after the LH surge or ovulatory hCG administration. However, little is known about the role of cortisol/glucocorticoid receptors in the ovulatory process and luteinization in humans.
STUDY DESIGN, SIZE, DURATION
This study was an experimental prospective clinical and laboratory-based study. An in vivo experimental study was accomplished utilizing the dominant ovarian follicles from 38 premenopausal women undergoing laparoscopic sterilization. An in vitro experimental study was completed using the primary human granulosa/lutein cells (hGLC) from 26 premenopausal women undergoing IVF.
PARTICIPANTS/MATERIALS, SETTING, METHODS
This study was conducted in a private fertility clinic and academic medical centers. Dominant ovarian follicles were collected before the LH surge and at defined times after hCG administration from women undergoing laparoscopic sterilization. Primary hGLC were collected from women undergoing IVF. hGLC were treated without or with hCG in the absence or presence of RU486 (20 µM; dual antagonist for progesterone receptor and glucocorticoid receptor) or CORT125281 (50 µM; selective glucocorticoid receptor antagonist) for 12 or 36 h. The expression of genes involved in glucocorticoid receptor signaling, steroidogenesis, and ovulatory cascade was studied with RT-quantitative PCR and western blotting. The production of cortisol, corticosterone, and progesterone was assessed by hormone assay kits.
MAIN RESULTS AND THE ROLE OF CHANCE
hCG administration upregulated the expression of hydroxysteroid 11-beta dehydrogenase 1 (HSD11B1), nuclear receptor subfamily 3 group C member 1 (NR3C1), FKBP prolyl isomerase 5 (FKBP5), and FKBP prolyl isomerase 4 (FKBP4) in human ovulatory follicles and in hGLC (P < 0.05). RU486 and CORT125281 reduced hCG-induced increases in progesterone and cortisol production in hGLC. The expression of genes involved in glucocorticoid receptor signaling, steroidogenesis, and the key ovulatory process was reduced by RU486 and/or CORT125281 in hGLC.
LARGE SCALE DATA
N/A.
LIMITATIONS, REASONS FOR CAUTION
The role of cortisol/glucocorticoid receptors demonstrated using the hGLC model may not fully reflect their physiological roles in vivo.
WIDER IMPLICATIONS OF THE FINDINGS
Successful ovulation and luteinization are essential for female fertility. Women with dysregulated cortisol levels often suffer from anovulatory infertility. Deciphering the functional role of glucocorticoid receptor signaling in human periovulatory follicles enhances our knowledge of basic ovarian physiology and may provide therapeutic insights into treating infertility in women.
STUDY FUNDING/COMPETING INTEREST(S)
This study was supported by P01HD71875 (to M.J., T.E.C., and M.B.) and R01HD096077 (to M.J.) from the Foundation for the National Institutes of Health and the BTPSRF of the University of Kentucky Markey Cancer Center (P30CA177558). The authors report no competing interests.
TRIAL REGISTRATION NUMBER
N/A.
Topics: Female; Humans; Progesterone; Receptors, Glucocorticoid; Hydrocortisone; Glucocorticoids; Prospective Studies; Mifepristone; Infertility, Female; Receptors, LH; Luteinization; Peptidylprolyl Isomerase
PubMed: 36752644
DOI: 10.1093/humrep/dead017 -
Reproduction (Cambridge, England) Mar 2020Bone morphogenetic proteins (BMPs) are known to play an indispensable role in preventing the precocious luteinization of granulosa cells within growing ovarian...
Bone morphogenetic proteins (BMPs) are known to play an indispensable role in preventing the precocious luteinization of granulosa cells within growing ovarian follicles. In this study, we found that the transcripts of BMP8 genes are enriched in the ovaries of humans and rodents. When analyzing transcriptomic datasets obtained from human mature granulosa cells, we further found that the BMP8 transcripts not only show the highest abundance among the searchable BMP-related ligands but also decrease significantly in women of advanced age or women with polycystic ovarian syndrome. The correlation between the BMP8 levels in granulosa cells and the decline in ovarian function in these subjects suggests that BMP8 protein may be involved in the regulation of granulosa cell function(s). Using a rat model, we demonstrated that human BMP8A protein activates the SMAD1/5/8 and the SMAD2/3 pathways simultaneously in both immature and mature granulosa cells. Furthermore, the expression of potential type I and type II receptors used by BMP8 in rat granulosa cells was characterized. We found that BMP8A treatment can significantly inhibit gonadotropin-induced progesterone production and steroidogenesis-related gene expression in granulosa cells. Pathway dissection using receptor inhibitors further revealed that such inhibitory effects occur specifically through the BMP8-activated SMAD1/5/8, but not SMAD2/3, pathway. Taken together, considering its abundance and possible functions in granulosa cells, we suggest that BMP8 may act as a novel luteinization inhibitor in growing follicles.
Topics: Animals; Bone Morphogenetic Proteins; Female; Granulosa Cells; Humans; Luteinization; Polycystic Ovary Syndrome; Rats, Sprague-Dawley; Smad Proteins; Superovulation
PubMed: 31940275
DOI: 10.1530/REP-19-0305