scholarly journals Pilot study: Alternative spliced variants of the Follicle-Stimulating Hormone Receptor gene in Greek women undergoing In Vitro Fertilisation (IVF)

2019 ◽  
Vol 18 (4) ◽  
pp. 155-162
Author(s):  
Eudoxia Mamas ◽  
Despoina Mavrogianni ◽  
Rami Raouasnte ◽  
Spyros Karkatzoulis ◽  
Emmanouela Liokari ◽  
...  
Keyword(s):  
Ovarian Stimulation ◽  
Hormone Receptor ◽  
Splice Variants ◽  
Receptor Gene ◽  
Ovarian Response ◽  
Cumulus Cells ◽  
Response To Treatment ◽  
In Vitro Fertilisation ◽  
Nucleotide Polymorphisms

Assisted Reproduction Technology (ART) has proven to be a valuable tool for infertile couples. Unfortunately, no perfect ovarian stimulation protocol has been designed and ovarian response shows great variability among women. Pharmacogenomics aims at detecting genetic markers so as to individualize protocols in order to maximize ovarian response to treatment. Follicle Stimulation hormone receptor (FSHR) mutations and single nucleotide polymorphisms have been extensively studied. Splice variants of the FSHR have been detected in women undergoing in vitro fertilisation (IVF). This study aims to determine the presence FSH splice variants in Greek women undergoing IVF. RNA was extracted from cumulus cells from 35 women and analysed by real time PCR. Splice variants were detected by gel electrophoresis. Three cases of deletion of exon 9 and 2 cases of insertion of intron 8 were detected in our study group. No association between the presence of splice variants and response to ovarian stimulation was detected. Two live births were detected one in each variant group. Even though these two types of splice variant detected do not show any clinical correlation it is believed that variants of the FSHR may be associated with poor or high response to exogenous gonadotrophin so further research is necessary.

331 EFFECT OF SUCESSIVE LAPAROSCOPIC OOCYTE RECOVERY AFTER HORMONAL TREATMENT IN CROSSBRED GOATS

2010 ◽  
Vol 22 (1) ◽  
pp. 321
Author(s):  
S. R. G. Avelar ◽  
K. C. Almeida ◽  
A. F. Pereira ◽  
F. C. Sousa ◽  
R. R. Moura ◽  
...  
Keyword(s):  
Ovarian Stimulation ◽  
Prostaglandin F2α ◽  
Hormonal Treatment ◽  
Ovarian Response ◽  
Cumulus Cells ◽  
Embryo Production ◽  
Hormonal Stimulation ◽  
Exact Test ◽  
Oocyte Recovery

Laparoscopic oocyte recovery (LOR) is a valuable tool for obtaining oocytes for in vitro embryo production. When preceded by a treatment of ovarian stimulation, this technique produces an increase in the amount of oocytes recovered. However, a little information has been found to respect the effect of successive hormonal treatments on both oocyte quantity and quality. Therefore, the objectives of this study were to evaluate the ovarian response and quantitative and qualitative COC production. Five adult crossbred goats were hormonally treated with intravaginal sponges containing 60 mg of medroxyprogesterone acetate (MAP, Progespon, Syntex, Buenos Aires, Argentina) for 11 days. In the 8th day of progestagen treatment, 50 μg of prostaglandin F2α analogue (Ciosin, Coopers, São Paulo, Brazil) was administered by i.m. injection. At this time, ovarian stimulation was initiated by the administration of 120 mg pFSH (Folltropin-V, Vetrepharm, Canada) distributed in five decreasing doses (30/30, 20/20, 20 mg), at 12-h intervals. The animals were fasted for 24 h before the laparoscopic procedure, which was performed just after the sponge removal. A laparoscopic system connected to a 22-gauge needle (WTA, Watanabe, Brazil) and a vacuum pump (Biovacuum, Biocom, Brazil) providing 30 mm Hg was used. All follicles with a size larger than 2 mm present in both ovaries were counted and aspirated. The collection medium was TCM-199 supplemented with HEPES (10 mM), heparin (20 IU mL-1), and gentamicin (40 μg mL-1). The COCs were graded based on presence of cumulus cells and cytoplasm homogeneity (I to IV). The hormonal treatment and LOR procedures were repeated three times at 14-day intervals. Data were expressed in percentage or mean ± SEM. The differences were analyzed using ANOVA and Tukey’s or Fischer’s exact test when appropriate, with P < 0.05. No statistical differences were found (P > 0.05) for the number of follicles obtained in each LOR session: 17.0 ± 3.91, 18.75 ± 2.59, and 18.0 ± 4.73, respectively. Repeated LOR procedures also did not affect (P > 0.05) the number of aspirated follicle (15.0 ± 3.92, 15.5 ± 2.33, and 16.0 ± 4.36), resulting from the three sessions, respectively. Average recovery rates were not statistically different (P > 0.05), resulting in 74.7%, 62.9%, and 64.6% between sessions. With respect to the percentage of viable COCs (GI and GII) were not observed statistical differences (P > 0.05), as verified the follow values at 1st to 3rd sessions: 76.79%, 84.62%, and 74.19%. In conclusion, three successive hormonal stimulation LOR procedures did not cause detrimental effects on quantitative and qualitative oocyte production, suggesting that this protocol can be used for programs of in vitro goat embryo production. This study was supported the following Brazilian agencies: FINEP, CNPq, FUNCAP, and CAPES.

scholarly journals Controlled ovarian hyperstimulation for poor ovarian responders undergoing in vitro fertilisation/intracytoplasmic sperm injection: a protocol for systematic review and Bayesian network meta-analysis

BMJ Open ◽  
2021 ◽  
Vol 11 (2) ◽  
pp. e039122
Author(s):  
Huisheng Yang ◽  
Chensi Zheng ◽  
Qiyan Zheng ◽  
Huanfang Xu ◽  
Xiaotong Li ◽  
...  
Keyword(s):  
Pregnancy Rate ◽  
Intracytoplasmic Sperm Injection ◽  
Ovarian Stimulation ◽  
Meta Analysis ◽  
Ovarian Response ◽  
Controlled Ovarian Hyperstimulation ◽  
In Vitro Fertilisation ◽  
Ovarian Hyperstimulation ◽  
Poor Ovarian Responders

IntroductionControlled ovarian hyperstimulation (COH) is the routine regimen used to generate a sufficient number of follicles during in vitro fertilisation (IVF) or intracytoplasmic sperm injection (ICSI) treatment. Poor ovarian response is a challenge encountered by many clinicians during COH and poor ovarian responders (PORs) usually have higher follicle stimulating hormone levels, lower levels of anti-Mullerian hormone and few oocytes retrieved, which have been attributed mainly to advanced maternal age and poor follicle reserve or other reasons that could impair ovarian response during ovarian stimulation. Over the last few decades, researchers have proposed a series of strategies and ovarian stimulation protocols to improve pregnancy outcomes in patients with POR during their IVF/ICSI treatment. However, clinical decisions regarding COH protocols in PORs during IVF/ICSI treatment remain controversial. Traditional pairwise meta-analysis only allows the direct comparison of two protocols in COH for patients with POR. However, many of these COH protocols have not been compared directly in randomised controlled trials (RCTs). Thus, we aim to use network meta-analysis (NMA) to assess the clinical effectiveness and safety of COH protocols and to generate treatment rankings of these COH protocols for the most clinically important and commonly reported outcomes events.Methods and analysisThe PubMed, Embase, Cochrane Library, Web of Science, SinoMed, CNKI, WanFang database and Chongqing VIP information databases will be searched for all RCTs of COH for POR women during IVF/ICSI from inception to 31 March 2020. Primary outcomes will include live birth rate and number of oocytes retrieved. Secondary outcomes will include ongoing pregnancy rate, clinical pregnancy rate, miscarriage rate, ovarian hyperstimulation syndrome rate, multiple pregnancy rate and cycle cancellation rate. Pairwise meta-analysis and Bayesian NMA will be conducted for each outcome. Subgroup analysis, meta-regression, and sensitivity analysis will be performed to assess the robustness of the findings. The generation of NMA plots and subsequent results will be performed by using R V.4.0.1. The assessment of confidence in network estimates will use the Confidence in Network Meta-Analysis)web application (see https://cinema.ispm.unibe.ch/).Ethics and disseminationThis review does not require ethics approval and the results of the NMA will be submitted to a peer-review journal.

scholarly journals Ex vivo Retrieval of Mature Oocytes for Fertility Preservation in a Patient with Bilateral Borderline Ovarian Tumor

2021 ◽  
Author(s):  
Bruno Ramalho de Carvalho ◽  
Geórgia Fontes Cintra ◽  
Taise Moura Franceschi ◽  
Íris de Oliveira Cabral ◽  
Leandro Santos de Araújo Resende ◽  
...  
Keyword(s):  
Fertility Preservation ◽  
Ovarian Stimulation ◽  
Ovarian Tumor ◽  
Ex Vivo ◽  
Oocyte Retrieval ◽  
Ovarian Response ◽  
Malignant Cell ◽  
Borderline Ovarian Tumor ◽  
Increased Risk

AbstractWe report a case of ultrasound-guided ex vivo oocyte retrieval for fertility preservation in a woman with bilateral borderline ovarian tumor, for whom conventional transvaginal oocyte retrieval was deemed unsafe because of the increased risk of malignant cell spillage. Ovarian stimulation with gonadotropins was performed. Surgery was scheduled according to the ovarian response to exogenous gonadotropic stimulation; oophorectomized specimens were obtained by laparoscopy, and oocyte retrieval was performed ∼ 37 hours after the ovulatory trigger. The sum of 20 ovarian follicles were aspirated, and 16 oocytes were obtained. We performed vitrification of 12 metaphase II oocytes and 3 oocytes matured in vitro. Our result emphasizes the viability of ex vivo mature oocyte retrieval after controlled ovarian stimulation for those with high risk of malignant dissemination by conventional approach.

Oestrogen receptor gene polymorphisms and ovarian stimulation for in- vitro fertilization

1997 ◽  
Vol 12 (7) ◽  
pp. 1430-1433 ◽  
Author(s):  
I. Georgiou ◽  
M. Konstantelli ◽  
M. Syrrou ◽  
I. E. Messinis ◽  
D. E. Lolis
Keyword(s):  
In Vitro Fertilization ◽  
Ovarian Stimulation ◽  
Gene Polymorphisms ◽  
Oestrogen Receptor ◽  
Receptor Gene ◽  
Vitro Fertilization ◽  
Receptor Gene Polymorphisms

scholarly journals Sperm binding to ZP2-coated beads improve the efficiency of porcine in vitro fertilisation

Reproduction ◽  
2020 ◽  
Vol 160 (5) ◽  
pp. 725-735
Author(s):  
Julieta Gabriela Hamze ◽  
María Jiménez-Movilla ◽  
Raquel Romar
Keyword(s):  
Acrosome Reaction ◽  
Cumulus Cell ◽  
Cumulus Cells ◽  
In Vitro Fertilisation ◽  
Sperm Binding ◽  
Fertilisation Rate ◽  
Gamete Recognition ◽  
Boar Spermatozoa

The role of specific zona pellucida (ZP) glycoproteins in gamete interaction has not yet been elucidated in many species. A recently developed 3D model based on magnetic sepharose beads (B) conjugated to recombinant ZP glycoproteins (BZP) and cumulus cells (CBZP) allows the study of isolated ZP proteins in gamete recognition studies. The objective of this work was to study the role of porcine ZP2, ZP3 and ZP4 proteins in sperm binding, cumulus cell adhesion and acrosome reaction triggering. ZP protein-bound beads were incubated with fresh ejaculated boar spermatozoa and isolated cumulus cells for 24 h. The number of sperm bound to the beads, the acrosomal shrouds (presence of acrosomal content) on the bead’s surface, and the acrosome integrity (by means of PNA-FITC lectin) in bound and unbound sperm were studied. Finally, in vitro matured porcine oocytes mixed with BZP2 were inseminated in vitro using fresh sperm and fertilisation results evaluated. Over 60% of beads had at least one sperm bound after 2 h of coincubation. ZP2-beads (BZP2) and cumulus-ZP2-bead complexes (CBZP2) reached the highest number of sperm per bead, whereas BZP3 and BZP4 models showed the highest number of unbound reacted sperm cells and acrosomal shrouds. Fertilisation efficiency and monospermy rate increased when oocytes were fertilised in the presence of BZP2. We, therefore, conclude that in pigs, it is mainly ZP2 that is involved in sperm-ZP binding whereas ZP3 and ZP4 induce acrosome reaction. Using magnetic sepharose ZP2-bound beads might be a valuable tool to improve the fertilisation rate in pigs.

scholarly journals Discovery and Preclinical Development of Orally Active Small Molecules that Exhibit Highly Selective Follicle Stimulating Hormone Receptor Agonism

2021 ◽  
Vol 11 ◽  
Author(s):  
Selva Nataraja ◽  
Henry Yu ◽  
Joie Guner ◽  
Stephen Palmer
Keyword(s):  
Ovarian Stimulation ◽  
Hormone Receptor ◽  
Ovulation Induction ◽  
Low Dose ◽  
Intrauterine Insemination ◽  
Follicle Stimulating Hormone ◽  
Controlled Ovarian Stimulation ◽  
Orally Active ◽  
Stimulating Hormone

An orally active follicle stimulating hormone receptor allosteric agonist would provide a preferred treatment for over 16 million infertile women of reproductive age in low complexity methods (ovulation induction-intrauterine insemination) or in high complexity methods (controlled ovarian stimulation-in vitro fertilization). We present two oral follicle stimulating hormone receptor allosteric agonist compounds that have the desired pharmacology, drug metabolism, pharmacokinetics, and safety profile for clinical use. These molecules provide a single agent suitable for ovulation induction-intrauterine insemination or controlled ovarian stimulation-in vitro fertilization that is more convenient for patients and achieves similar preclinical efficacy as rec-hFSH. TOP5668, TOP5300 were evaluated in vitro in Chinese hamster ovary cells transfected with individual glycoprotein receptors measuring cAMP (FSHR, LH/CGR, thyroid stimulating hormone receptor). TOP5668 was found to have solely follicle stimulating hormone receptor allosteric agonist activity while TOP5300 was found to have mixed follicle stimulating hormone receptor allosteric agonist and LHR-AA activity. Both compounds stimulated concentration-dependent increases in estradiol production from cultured rat granulosa cells in the presence or absence of low dose rec-hFSH, while only TOP5300 stimulated testosterone production from rat primary Leydig cells. In pooled human granulosa cells obtained from patients undergoing controlled ovarian stimulation-in vitro fertilization, TOP5300 stimulated 7-fold greater maximal estradiol response than rec-hFSH and TOP5668 was 10-fold more potent than TOP5300. Both TOP5300 and TOP5668 stimulated follicular development in immature rat to the same efficacy as recombinant follicle stimulating hormone. In mice treated with TOP5300, in the presence of low dose of follicle stimulating hormone, there were no differences in oocyte number, fertilization rate, and hatched blastocyst rate in mice with TOP5300 and low dose follicle stimulating hormone vs. reference proteins pregnant mare serum gonadotropin or high dose rec-hFSH. ADME/PK and safety profiles were favorable. In addition, there was no appreciable activity on thyroid hormones by TOP5300 in 14-days toxicological study in rat or dog. The selected lead compound, TOP5300 stimulated a more robust increase in estradiol production from granulosa-lutein cells from women with polycystic ovarian syndrome patient compared to rec-hFSH. Conclusions: Two novel oral FSHR allosteric agonist, TOP5668 and TOP5300, were found to mimic the biological activity of rec hFSH in preclinical studies. Both compounds led to folliculogenesis and superovulation in rat and mice. Specifically, TOP5300 led to a similar number of ovulated oocytes that fertilized and developed into hatched blastocysts in mice when compared to rec-hFSH. The safety profile demonstrated lack of toxicity.

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