In vitro oocyte maturation (IVM) is an assisted reproductive technology requiring minimal or no ovarian stimulation. In this technique, the immature oocytes were retrieved from follicles and subsequently cultured matured, meaning that GV oocytes reached MII in vitro (ASRM, 2021).
Currently, there is no consensus on the unique IVM protocol. However, recommended protocols that are being utilized include IVM with and without hCG (Standard IVM) and CAPA-IVM.
As mentioned previously, FSH priming before oocyte retrieval for IVM remains controversial. However, FSH is known as a hormone for the maturation of the follicles. Therefore, during oocyte maturation (IVM) cycles, FSH is used to "prime" follicular development. Generally, many studies showed a trend of a higher number of MII oocytes obtained after IVM after using FSH priming.
In animal models, Younis et al. (1994) observed a significant increase in the number of mature oocytes when performing IVM in cynomolgus monkeys (Macaca fascicularis) with a dose of 1000 IU of PMSG (pregnant mare's serum gonadotropin) in the follicular phase (Younis et al., 1994). Similarly, Wynn et al. (1998) conducted a study on mice. The results from this study revealed that a higher number of MII oocytes was observed. Still, the blastulation rate and the number of blastomeres were significantly lower than that without FSH priming. On the other hand, FSH activates meiosis resumption (Wynn et al., 1998).
In addition, an RCT of 28 patients comparing three days of 150 IU of FSH before the IVM aspiration group with the control group also showed an improvement in implantation rates in IVM cycles with FSH priming (Mikkelsen et al., 2001). The studies mentioned above both used the non-hCG IVM protocol. Other studies by Shalom-Paz et al. (2011) and Choavaratana et al. (2015) showed superiority in the number of MII oocytes.
There has been no data on the impact of not using FSH priming in CAPA-IVM cycles. Therefore, this RCT will investigate the efficacy of CAPA-IVM with and without FSH priming.

开始日期2023-01-02

申办/合作机构-

NCT03856268 / WithdrawnN/AIIT

Understanding the Roles of Estradiol and Follicle-stimulating Hormone in Adipocyte Remodeling Following Surgical and Pharmacology-induced Menopause (RESUME-2 Study)

The overarching aims of this study are to:
1. Characterize the rate of in vivo adipogenesis, and changes in adipose tissue gene and protein expression, in the scABD and scFEM depots of women undergoing surgical menopause (↓E2, ↑FSH).
2. Characterize the rate of in vivo adipogenesis, and changes in adipose tissue gene and protein expression, in the scABD and scFEM depots of women undergoing gonadal suppression (↓E2, ↓FSH).

开始日期2019-04-01

申办/合作机构

Pennington Biomedical Research Center

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100 项与促卵泡激素缺乏相关的临床结果

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100 项与促卵泡激素缺乏相关的转化医学

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项与促卵泡激素缺乏相关的文献（医药）

2024-09-01·Fertility and Sterility

Pulsatile gonadotropin-releasing hormone therapy: comparison of efficacy between functional hypothalamic amenorrhea and congenital hypogonadotropic hypogonadism

Article

作者: EVERAERE, Hortense ; DECANTER, Christine ; SIMON, Virginie ; LEROY, Maxime ; Simon, Virginie ; Dewailly, Didier ; Robin, Geoffroy ; Everaere, Hortense ; BACHELOT, Anne ; CATTEAU-JONARD, Sophie ; Bachelot, Anne ; Catteau-Jonard, Sophie ; DEWAILLY, Didier ; ROBIN, Geoffroy ; Leroy, Maxime ; Decanter, Christine

OBJECTIVETo compare the ongoing pregnancy rate per initiated cycle between patients with functional hypothalamic amenorrhea (FHA) and patients with congenital hypogonadotropic hypogonadism (CHH) treated with pulsatile gonadotropin-releasing hormone (GnRH) administration.DESIGNRetrospective monocentric cohort study conducted at the University Hospital of Lille from 2004 to 2022.SETTINGLille University Hospital, Department of Endocrine Gynecology.PATIENT(S)A total of 141 patients diagnosed with central suprapituitary amenorrhea during infertility evaluation and subsequently treated with pulsatile GnRH therapy. 111 and 30 patients were diagnosed with FHA or CHH, respectively.INTERVENTION(S)Pulsatile GnRH administration.MAIN OUTCOME MEASURE(S)Ongoing pregnancy rate per initiated cycle.RESULT(S)Ongoing pregnancy rates per initiated cycle were comparable between groups: 21.5% in the FHA group vs. 22% in the CHH group. Comparison of baseline characteristics showed a more pronounced follicle-stimulating hormone (FSH) deficiency in patients with CHH than in those with FHA: 2.55 (0.6-4.92) vs. 4.80 (3.90-5.70) UI/L. Within the CHH group, basal FSH level was positively associated with the occurrence of ongoing pregnancies (odds ratio, 1.57; 95% confidence interval, 1.11-2.22). In the CHH group, the duration of treatment was higher than in the FHA group: 23.59 (± 8.02) vs. 18.16 (± 7.66) days.CONCLUSION(S)The baseline FSH level is lower in patients with CHH than in patients with FHA. The lower the FSH, the lower the chance of pregnancy in patients with CHH. These patients also require more days of GnRH administration. However, the rate of ongoing pregnancies is comparable between the two groups.

2024-05-27·Endocrinology

A Dose-Response Study on Functional and Transcriptomic Effects of FSH on Ex Vivo Mouse Folliculogenesis

Article

作者: Zhan, Tingjie ; Douglas, Nataki C ; Chemerinski, Anat ; Zhang, Jiyang ; Zhao, Qingshi ; Zhang, Qiang ; Zhang, Ying ; Xiao, Shuo

AbstractFollicle-stimulating hormone (FSH) binds to its membrane receptor (FSHR) in granulosa cells to activate various signal transduction pathways and drive the gonadotropin-dependent phase of folliculogenesis. Both FSH insufficiency (due to genetic or nongenetic factors) and FSH excess (as encountered with ovarian stimulation in assisted reproductive technology [ART]) can cause poor female reproductive outcomes, but the underlying molecular mechanisms remain elusive. Herein, we conducted single-follicle and single-oocyte RNA sequencing analysis along with other approaches in an ex vivo mouse folliculogenesis and oogenesis system to investigate the effects of different concentrations of FSH on key follicular events. Our study revealed that a minimum FSH threshold is required for follicle maturation into the high estradiol-secreting preovulatory stage, and such threshold is moderately variable among individual follicles between 5 and 10 mIU/mL. FSH at 5, 10, 20, and 30 mIU/mL induced distinct expression patterns of follicle maturation–related genes, follicular transcriptomics, and follicular cAMP levels. RNA sequencing analysis identified FSH-stimulated activation of G proteins and downstream canonical and novel signaling pathways that may critically regulate follicle maturation, including the cAMP/PKA/CREB, PI3K/AKT/FOXO1, and glycolysis pathways. High FSH at 20 and 30 mIU/mL resulted in noncanonical FSH responses, including premature luteinization, high production of androgen and proinflammatory factors, and reduced expression of energy metabolism-related genes in oocytes. Together, this study improves our understanding of gonadotropin-dependent folliculogenesis and provides crucial insights into how high doses of FSH used in ART may impact follicular health, oocyte quality, pregnancy outcome, and systemic health.

2023-10-01·Pituitary

Giant prolactinomas, a detailed analysis of 196 adult cases.

Review

作者: Carlien, De Herdt ; Arno, Verleye ; Heyning Paul, Van de ; Christophe, De Block ; Lisa, Billion

PURPOSEGiant prolactinomas are a rare entity, representing approximately 5% of all prolactinomas. A systematic review of 196 adult cases was performed. A comparison of the clinical, biochemical and radiological characteristics, management and therapeutic outcomes in men versus women is made.METHODSA structured search was conducted using the term 'giant prolactinoma'. Following inclusion criteria were used: diameter ≥ 40 mm, prolactin levels > 1000 ng/ml and no concomitant GH/ ACTH secretion.RESULTS196 cases were included [age: 38 (28-50) years, F/M ratio: 1/3.6]. Median tumor diameter was 53 (43-69) mm. Pituitary deficiency was present in 91% of cases, with hypogonadotropic hypogonadism being the most frequent. Most common presenting symptoms were visual impairment (73%) and headache (50%) in men and amenorrhea (58%) in women. 82% of cases were treated with a dopamine agonist (DA) as first-line treatment which led to normoprolactinemia, tumor shrinkage and visual improvement in 51%, 88% and 85% of cases, respectively. Surgery was performed in 29% of cases and all showed tumor remnant and persistent hyperprolactinemia. Women had a lower prolactin level and a smaller tumor diameter at diagnosis but pituitary deficiencies were more frequent and outcome was worse.CONCLUSIONGiant prolactinomas are rare and have a male predominance. Visual impairment is the most frequent presenting symptom in men and amenorrhea in women. The gender-related difference in tumor size and level of prolactin was confirmed in this analysis where men had a larger diameter and a higher baseline prolactin level. DAs are the treatment of choice, irrespective of tumor size and presence of visual impairment. As only half of the cases achieved normoprolactinemia we do not, in contrast to previous literature, state giant prolactinomas to be exquisitely sensitive to DAs. Patient characteristics associated with persistent hyperprolactinemia after treatment with a DA were female gender, higher baseline prolactin and larger tumor size . This analysis did show TSH- and ACTH-deficiency to be more frequent after surgery which was not seen for LH/FSH deficiency.

项与促卵泡激素缺乏相关的新闻（医药）

2024-08-08

·PRNewswire

Gameto Announces Path Towards a U.S. Phase 3 Trial and Executive and Advisor Appointments

NEW YORK, April 9, 2024 /PRNewswire/ -- Gameto, a female-led biotechnology company with a mission to redefine women's healthcare, today provided an update on its clinical program for their lead asset, Fertilo, their novel investigational in vitro maturation (IVM) solution containing engineered ovarian support cells (OSC-IVM) to mature eggs outside of the body, and recent additions to its management team and scientific and clinical advisors. Clinical highlights Following productive discussions with the U.S. Food and Drug Administration (FDA), Gameto received tentative approval to proceed to Phase 3 trials, subject to the completion of certain assay and manufacturing requirements. This Phase 3 trial is a critical step toward a Biologic License Application (BLA) approval, with pregnancy assessed at 12 weeks of gestation as the primary efficacy endpoint. "This is a significant milestone in our journey to bring innovative treatment options to patients, and we are fully committed to meeting the rigorous standards set by the FDA to advance our product through the final phases of clinical development," said Dr. Dina Radenkovic, Chief Executive Officer and co-founder of Gameto. "IVF is a relatively new field and navigating the regulatory pathways in this industry poses unique challenges. We are grateful to the agency for their guidance and excited to have a defined path towards a potential BLA approval and market authorization in the U.S." As part of its discussions with the FDA, Gameto submitted preclinical animal data showing use of Fertilo did not lead to abnormalities in live births of mice. Mice born from eggs matured with Fertilo showed no genetic, developmental, or behavioral abnormalities, and overall no significant differences between live births compared to traditional IVM. Gameto presented these initial results at the 2023 American Society for Reproductive Medicine Congress. The manuscript describing these data is available on a preprint server at https://www.biorxiv.org/content/10.1101/2024.04.04.588122v1 and Gameto is submitting it for scientific peer-review for potential publication. Strengthened management team with appointment of Carlos Lejtik, M.D., as Medical Director Dr. Lejtik is a gynecologist and obstetrician, specializing in human reproduction, with over 20 years of experience. He leads the clinical adoption and medical teams at Gameto. Prior to Gameto, he had extensive experience in Medical Management at Pfizer. While at Pfizer, he planned and developed in-person and digital medical education programs for primary care physicians and specialists, collaborated with national and international key opinion leaders to develop diagnostic guidelines for various medical specialties (e.g., Women's Health, Contraception, Oncology, Central Nervous System, Dermatology, Infectious Diseases, Vaccination, and Rheumatology), successfully launched and positioned female health products such as "Duavive and Sayana," and established relationships with key associations, colleges, and medical boards. Welcoming leading reproductive medicine experts Pietro Bortoletto, M.D., M.Sc., and Michel de Vos, M.D., Ph.D., as scientific and clinical advisors Dr. Bortoletto is a board-certified reproductive endocrinologist. He is currently a Reproductive Medicine Specialist, Director of Reproductive Surgery, and Co-Director of Oncofertility Program at Boston IVF in Boston, Massachusetts. He is on staff at the Beth Israel Deaconess Medical Center Department of Obstetrics & Gynecology and a clinical instructor at the Harvard Medical School. In addition to his clinical role, Dr. Bortoletto currently serves as the Interactive Associate in Chief for Fertility & Sterility as well as Media Editor for F&S Reports. Dr. de Vos has worked as a gynecologist since 2006 and currently is a senior medical director at the Centre for Reproductive Medicine at Universitair Ziekenhuis Brussel, Belgium and an associate professor in reproductive medicine at Vrije Universiteit Brussel. In 2011, ESHRE and the European Board and College of Obstetrics and Gynaecology (EBCOG) recognized him as a subspecialist in reproductive medicine and surgery. He is a principal investigator of the FOTO (Freezing Ovarian Tissue and Oocytes) consortium, encompassing oncofertility research projects at three universities in Brussels: Vrije Universiteit Brussel (VUB), Université Libre de Bruxelles (ULB) and Université Catholique de Louvain (UCL) and he is a founding member of the Belgian Fertility Education Initiative (BFEI). "We are excited to welcome Carlos, Pietro, and Michel to the Gameto team," added Dr. Christian Kramme, Chief Scientific Officer of Gameto. "All three bring deep expertise in human reproduction, endocrinology, and women's health. They will be instrumental as Gameto enters commercial markets around the world, accelerates its growth and prepares to meet the FDA's conditions for Phase 3 trial initiation. Their experience is a great complement to our team and will help us realize our mission of filling the massive gaps in fertility medicine and improving the female reproductive journey." About Fertilo Fertilo, Gameto's lead investigational program, is a solution derived from induced pluripotent stem cells (iPSC) and designed to mature eggs outside of the body as part of minimal hormonal stimulation cycles for in vitro fertilization and egg freezing. Gameto's goal in developing Fertilo is to make fertility treatments more convenient, safer, and accessible for a wider patient population. Fertilo has received different regulatory classifications in foreign jurisdictions, and after consultation with national regulators, has been cleared for commercialization in Australia and in large markets in Latin America. About Gameto Gameto is a biotechnology company developing novel treatment solutions for women's health, starting with infertility. Gameto brings together an experienced scientific management team with the vision and passion to develop a product suite to support women throughout their reproductive journeys. Gameto's lead program, Fertilo, aims to make IVF and egg freezing shorter, safer, and more accessible through reduced hormonal injections by maturing eggs outside of the body. Gameto is led by physician-turned-entrepreneur Dina Radenkovic as CEO and serial entrepreneur and founder of North America's largest fertility network Prelude Fertility, Martin Varsavsky, as Chairman. For more information, go to gametogen.com or follow us on Twitter and Instagram @gametogen and on LinkedIn.

临床3期高管变更