Dose Of Follicle-stimulating Hormone Research Articles

A predictive formula for selecting individual FSH starting dose based on ovarian reserve markers in IVF/ICSI cycles.

Although exogenous follicle-stimulating hormone (FSH) has been used for decades and millions of cycles have been performed worldwide until now, criteria for selecting the proper FSH starting dose have not been clearly identified. The aim of this study was to elaborate a formula based on markers of ovarian reserve for the calculation of the appropriate starting dose of FSH. A total of 931 patients underwent in vitro fertilization (IVF) treatment using long GnRH agonist protocol was retrospectively identified and reviewed. 673 cases of them with a normal ovarian response (4-14 retrieved oocytes) were used to analysis the predictive formula. All follicles 4-7mm in diameter were counted in the same day of blood sample in both ovaries using transvaginal ultrasound scan. The modified protocol of each patient was recorded and analyzed in the same center. In another center were the numbers of retrieved oocytes of 750 validated patients recorded and analyzed. A formula model based on age, AMH, and antral follicle count (AFC) was able to accurately predict the ovarian sensitivity and accounted for 57.2% of the variability of ovarian response to FSH. When tested in the same total population used to elaborate the model it predicts a high 46.88% rate of step-down protocol in higher-starting FSH dose group and about 57.92% of patients had their dose step-up modified in lower-starting FSH dose group during their treatment, respectively. And when tested in different population from another center used to elaborate the model it predicts a high 64.40% rate of ≥ 15 retrieved oocytes in higher-starting FSH dose group and about 22.50% of patients had ≤ 7 retrieved oocytes in lower-starting FSH dose group during their treatment, respectively. In the present study we demonstrated that the individualized FSH starting dose may be calculated on the basis of a woman's age, AMH and AFC. The formula model might be a useful, immediate, and easily applicable tool for clinicians to predict the tailored starting dose of FSH during their daily clinical practice.

Alternative Follicle Stimulating Hormone Dose Rate for Embryo Production in Dairy Cattle

Alternative Follicle Stimulating Hormone Dose Rate for Embryo Production in Dairy Cattle

Predictive factors for biochemical pregnancy in intracytoplasmic sperm injection cycles

The aim of this study was to investigate which factors contribute to the incidence of biochemical pregnancy (BP) in intracytoplasmic sperm injection (ICSI) cycles. This cohort study included cycles performed from June 2010 to September 2016 in a private, university-affiliated IVF centre. Cycles were split into four groups, depending on the pregnancy outcomes: Clinical Pregnancy (CP, n = 903), Biochemical Pregnancy (BP, n = 55), Miscarriage (MI, n = 142) and Negative Pregnancy (NP, n = 2034). The effects of ovarian stimulation, laboratory data and seminal parameters on pregnancy outcomes were evaluated using adjusted general linear models. Discriminant analyses were conducted to construct a model for pregnancy prediction and to establish cut-offs for BP. The total sperm count (p = 0.035), total and progressive sperm motility (p = 0.001 and p = 0.023, respectively), total motile sperm count (TMSC, p = 0.029) and the endometrial thickness (p < 0.001) were lower among BP group cycles. Lower rates of high-quality cleavage-stage embryos were observed in the BP group compared to CP and MI groups (p < 0.001). In discriminant analyses, cut-offs for BP prediction were established for the following factors: endometrial thickness < 11 mm, sperm motility < 55.5% and total dose of follicle-stimulating hormone (FSH)> 2400 IU. The incidence of biochemical pregnancy was four times higher when the aforementioned factors did not meet the defined cut-offs. The combination of suboptimal endometrial development and poor seminal and embryo quality contribute to an increased incidence of biochemical pregnancy in ICSI cycles.

A high dose of total recombinant FSH suppresses granulosa cell apoptosis and maintains oocyte quality in endometriosis: A cross-sectional study

Background: Endometriosis is one of the most common conditions causing infertility and an indication to undergo in vitro fertilization (IVF). High apoptosis rate and oxidative stress in patients with endometriosis are believed to negatively affect the IVF success rate. However, there have been conflicting results on the effect of endometriosis on IVF success, and there have been limited studies that directly assess endometriosis and its effect on oocyte quality. This study was performed to explore the correlation between mRNA BAX/BCL-2 expression and oocyte quality in endometriosis compared to non-endometriosis subjects. Methods: This was a cross-sectional study. 15 endometriosis and 15 non-endometriosis subjects were recruited through convenience sampling at Cipto Mangunkusumo Hospital, Jakarta. All subjects underwent follicle stimulation with recombinant follicle-stimulating hormone (FSH). Granulosa cells were collected and tested for BAX and BCL-2 expression and the results were compared to the oocyte quality and fertilization rate of the patients. Results: The total dose of recombinant FSH received by the endometriosis group was significantly higher compared with that of the non-endometriosis group (p = 0.005). There was a difference in BAX level (p = 0.029) and BCL-2 level (p&lt;0.001) between groups. However, the BAX/BCL-2 ratio did not differ significantly (p = 0.787) between groups. No significant correlation was found between the BAX/BCL-2 ratio and any of the oocyte quality parameters measured. Conclusion: We found that there is a significantly higher dose in total dose recombinant FSH received by the endometriosis group compared with the non-endometriosis group. We also found that there was no significant difference in BAX/BCL-2 ratio between the endometriosis and non-endometriosis groups.

199 The effect of different doses of follicle-stimulating hormone during superovulation on ovarian function in dairy cattle

Cattle with an unknown antral follicle count (AFC) during follicular waves respond to different FSH doses during superovulation in a curvilinear fashion with the highest doses decreasing or not increasing ovulatory follicle number, number of transferable embryos, and number of corpora lutea (CL). These observations support the hypothesis that heifers treated with different FSH doses during superovulation will reach a superovulation maximum (SOVmax) and that doses exceeding SOVmax are excessive, resulting in a decrease in ovarian function. To test this hypothesis, we used eight 12-month-old Holstein heifers with a low AFC (&amp;lt;10 follicles ≥3mm in diameter, index for small ovarian reserve). These 8 heifers were subjected to 4 different superovulations with a 21-day intervals between each superovulation. During each superovulation, which began on Day 1 of a synchronized oestrous cycle before selection of a dominant follicle, 2 of the 8 heifers were treated (twice-daily FSH injections×4 days) with 20, 40, 80, or 120mg of Folltropin-V (Vetoquinol, Lure, France). At the end of the study, the same 8 heifers had been superovulated 4 times with each of the 4 FSH doses. To enhance ovulation rate in response to hCG, each superovulated heifer was injected with 3 different injections of prostaglandin F2α (PGF2α) spaced 12h apart to induce luteolysis of the original CL. Two PGF2α injections were given after each FSH injection on the last day of FSH treatment and the last PGF2α injection was given after the hCG (2500IU) injection, which was 12h after the last FSH injection. Daily ultrasonography was used to measure AFC and number of ovulatory follicles and CL during the study. Results of t-test analysis showed that at time of hCG, AFC was greater (P&amp;gt;0.05) for heifers treated with the 40-mg (mean±s.e.m., 27±3.7) v. 20-mg (17.9±2.5) FSH dose, but the response to higher FSH doses (27.9±4.4; 27±3.3) did not differ from the response to the 40-mg dose. Number of ovulatory follicles was greater (P&amp;lt;0.05) for heifers treated with the 40-mg (17.5±2.3) v. 20-mg (10.1±1.4) FSH dose, but the response to higher doses (18.9±3.3; 17.3±2.4) did not differ from the response to the 40-mg dose. At Day 7 post-hCG, CL number was greater (P&amp;lt;0.05) for heifers treated with the 40-mg (13.8±2.9) v. 20-mg (7.4±1.4) dose, but response to higher doses (9.9±3.2; 9.1±2.3) did not differ from the response to the 40-mg dose. Ovulation rate (ovulatory follicle number divided by CL number) was greater (P&amp;lt;0.05) for heifers treated with the 40-mg (79±0.08%) v. 80-mg (52±0.09%) or 120-mg (53±0.09%) dose, but similar to that of heifers treated with 20-mg (73±0.09%) FSH dose. These results support the conclusion that the 40-mg FSH dose achieves SOVmax and FSH doses greater than SOVmax in cattle with a low AFC and small ovarian reserve are excessive and detrimental to ovarian function. This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2017-67015-26084 from the USDA National Institute of Food and Agriculture (Washington, DC).

191 The effect of high and low doses of follicle-stimulating hormone on embryo collection in Romanov sheep

The use of embryo transfer in small ruminants has served as a way of increasing superior female genetics. This technique, although not new, has been adopted by an increasing number of breeders over the past few years. The Romanov sheep breed is considered a natural litter-bearing breed compared with other small ruminant species, which generally have only 1 or 2 offspring during a natural parturition. This experiment was designed to evaluate the effect of FSH dosage on embryo production and collection in Romanov sheep. Sheep donors (n=12), with an average age of 2±1.4 years and an average body weight of 43±6.7kg, were randomly assigned to either a high (175mg) or low (140mg) dosage treatment of FSH during the breeding season. Hormone injections were given in a decreasing dosage twice daily over a period of 5 days. Donors were naturally cycling before being subjected to a CIDR-G protocol for a period of 15 days, with hormone injections beginning on Day 11. Donors were mated with rams (n=2) of known fertility for a total of 3 hand matings. After the third hand mating, the ram was turned into the breeding pen with the ewes. Embryos were collected 7 days after breeding and evaluated for transfer. A one-way ANOVA was utilised to analyse statistical differences between groups with significance set at (0.05). Results are given as mean±s.e.m. Only embryos of quality grades 1 and 2 were transferred during this study. No differences were detected between the 2 groups for total embryos collected between both high (7.6±6) and low (6.6±5) FSH groups. Furthermore, no differences were detected between both high and low FSH groups for the number of embryos transferred (5.6±5 and 6.3±4, respectively). The results of this study suggest that a lower total dosage (140mg) of FSH can be used in superovulation programs of Romanov ewes without affecting the total number of embryos collected and transferred. However, further investigation should be performed with various levels of FSH to determine the most accurate dosage for Romanov sheep.

A multi-center, randomized controlled clinical trial of the application of a shortened protocol of long-acting Triptorelin down-regulated prior to IVF/ICSI among patients with endometriosis: A protocol

BackgroundEndometriosis is the major cause of progressive pelvic pain and subfertility. Up to 50% of reproductive-age women suffer from pelvic pain. Endometriosis is a classic indication for IVF. Compared with women whose inability to procreate is caused by simple tubal infertility, women with endometriosis often have lower pregnancy rates following in vitro fertilization/intracytoplasmic sperm injection (IVF/ICSI). The administration of gonadotrophin-releasing hormone (GnRH) agonists prior to IVF/ICSI can improve the successful pregnancy rate. Whether a briefer treatment interval would be efficacious has not been studied.Methods/designEligible and consenting women will be randomly assigned to one of two treatments (one cycle of a GnRH agonist or two cycles of a GnRH agonist) prior to IVF/ICSI using a table of random numbers. The primary outcome of this trial is clinical pregnancy rate. Other outcomes include gonadotrophin (Gn) duration, the total dose of follicle-stimulating hormone (FSH) used, number of oocytes retrieved, number of embryos available for transfer, implantation rate, the abortion rate, live birth rate, and incidence of moderate-to-severe ovarian hyperstimulation. The sample size of this trial is estimated to be 421 participants for each of the two arms. Appropriate interim analyses will be conducted by a data monitoring and ethics committee (DMEC), and the final test will be an intention-to-treat analysis.Trial registrationThis trial has been assigned the following registry number: NCT03006406.

Specific protocols of controlled ovarian stimulation for oocyte cryopreservation in breast cancer patients.

Fertility preservation is an important concern in breast cancer patients. In the present investigation, we set out to create a specific protocol of controlled ovarian stimulation (cos) for oocyte cryopreservation in breast cancer patients. From November 2014 to December 2016, 109 patients were studied. The patients were assigned to a specific random-start ovarian stimulation protocol for oocyte cryopreservation. The endpoints were the numbers of oocytes retrieved and of mature oocytes cryopreserved, the total number of days of ovarian stimulation, the total dose of gonadotropin administered, and the estradiol level on the day of the trigger. Mean age in this cohort was 31.27 ± 4.23 years. The average duration of cos was 10.0 ± 1.39 days. The mean number of oocytes collected was 11.62 ± 7.96 and the mean number of vitrified oocytes was 9.60 ± 6.87. The mean estradiol concentration on triggering day was 706.30 ± 450.48 pg/mL, and the mean dose of gonadotropins administered was 2610.00 ± 716.51 IU. When comparing outcomes by phase of the cycle in which cos was commenced, we observed no significant differences in the numbers of oocytes collected and vitrified, the length of ovarian stimulation, and the estradiol level on trigger day. The total dose of follicle-stimulating hormone and human menopausal gonadotropin administered was statistically greater in the group starting cos in the luteal phase than in the group starting in the late follicular phase. Our results suggest that using a specific protocol with random-start ovarian stimulation for oocyte cryopreservation in breast cancer patients is effective and could be offered to young women undergoing oncologic treatment.

Effect of insulin or insulin-like growth factor-I administration at mid-luteal phase of the estrous cycle during superovulation on hormonal profile of Sahiwal cows.

Aim:The present study was designed to study the effect of insulin and insulin-like growth factor-1 (IGF-I) administration during luteal phase of the estrous cycle on the hormonal profile of Sahiwal embryo donor cows during superovulation.Materials and Methods:Cows (n=18) were selected and divided into three groups; control (n=6, untreated), T-I (n=6, insulin-treated), and T-II (n=6, IGF-I treated). Insulin and IGF-I were given S/C on 5th, 6th, 7th, and 8th days of estrous cycle. Superovulatory treatment was started on day 9th of the estrous cycle. With the sixth dose of follicle-stimulating hormone, prostaglandin was injected to induce superovulatory heat. The superovulated cows were bred, and superovulatory response of each animal was recorded. The embryos were collected non-surgically on the 7th day of superovulatory estrus. About 15 ml blood without anticoagulant was collected on days 5, 7, 9, 11, 13, 15, 17, 19, and 21 or day of embryo recovery where day 0 of estrous cycle was taken as day of estrus. Serum was separated, centrifuged, and transferred into sterilized serum vials. All samples were stored at −20°C till analysis. Progesterone, insulin, and IGF-I were estimated in blood serum by radioimmunoassay using radioimmunoassay kits.Results and Discussion:The mean concentration of progesterone on days 7 and 11, insulin on days 7 and 9, and IGF-I on days 5, 7, 9, 11, and 15 was significantly higher in insulin-treated T-I groups as compared to untreated control.Conclusion:It may be concluded that exogenous insulin administration during mid-luteal phase may be helpful in follicular and embryonic development through modulation of progesterone, insulin, and IGF-I in indigenous (Bos indicus) Sahiwal embryo donor cows.

A simplified superovulation protocol using split-single administration of Folltropin®-V in hyaluronan: application to purebred sheep

Superovulation is an important step in assisted reproductive technology. Due to its short half-life, follicle stimulating hormone is usually given twice daily to ewes for three to five days, which is both time- and labour-intensive. However, dissolving follicle stimulating hormone in degradable polymers to delay absorbtion has been effective in ruminants. Experiment 1 was performed to compare a split-single follicle stimulating hormone dissolved in hyaluronan (S group; 150 mg follicle stimulating hormone on the first day and 30 mg 48 h later; n = 21) and six decreasing doses of follicle stimulating hormone (M group; 50, 50, 30, 30, 10 and 10 mg; n = 22) at 12-h intervals. Ovarian responses and numbers of recovered ova/embryos did not differ significantly between groups. However, there tended to be more Grade 1 and 2 embryos in S vs M groups (mean ± SEM, 5.1 ± 4.9 vs 2.9 ± 2.9, respectively; P = 0.08). Experiment 2 tested the effectiveness of a simplified split-single follicle stimulating hormone in purebred sheep on a commercial farm. The numbers of recovered good-grade embryos (day 2) were 4.8 ± 5.0 and 4.0 ± 2.5 per donors in Corriedale and Bond sheep breeds, respectively. We conclude that this modified technique for ewe superovulation improved animal welfare, reduced animal handling and labour and yielded results similar to or better than conventional twice-daily follicle stimulating hormone treatments.

Pilot study of the optimal protocol of low dose step-up follicle stimulating hormone therapy for infertile women.

PurposeTo evaluate the optimized protocol of low dose follicle‐stimulating hormone (FSH) therapy that has a starting dose of 50 IU/62.5 IU with a small increment dose (12.5 IU) for women with World Health Organization (WHO) II ovulatory disorder and unexplained infertility.MethodsAnovulatory women with WHO group II ovulatory disorder (ovulation induction [OI] patients, n = 29), and with an unexplained infertility (ovarian stimulation [OS] patients, n = 21) were enrolled. The protocol of low dose step‐up FSH therapy was optimized for the starting dose as 50 IU (body mass index [BMI] < 20 group) and 62.5 IU (BMI ≥ 20 group) with the increment dose of 12.5 IU. Study outcomes were ovulation, monofollicular development and other variables.ResultsIn the OIpatients, the ovulation rate was 100% (BMI < 20 group) and 90.9% (BMI ≥ 20 group). Monofollicular development was 80.0% (BMI < 20) and 77.3% (BMI ≥ 20). The pregnancy rate was 60% (3/5 BMI < 20) and 18.2% (4/22 BMI ≥ 20). There was no multiple pregnancy. In the OSpatients, the ovulation rate was 100%. Monofollicular development was 85.7% (BMI < 20) and 76.6% (BMI ≥ 20). No pregnancy was achieved in the OSpatients.ConclusionOptimized protocol of low dose FSH therapy setting a starting dose 50 IU/62.5 IU by BMI with an increment dose of 12.5 IU was safe and highly effective in WHO group II anovulatory patients. However, this protocol seemed uneffective for patients with unexplained infertility.

MP07-11 ANALYSIS OF THE CLINICAL AND COST-EFFECTIVENESS OF COMPOUNDED FSH FOR MALE INFERTILITY TREATMENT

You have accessJournal of UrologyInfertility: Therapy II1 Apr 2018MP07-11 ANALYSIS OF THE CLINICAL AND COST-EFFECTIVENESS OF COMPOUNDED FSH FOR MALE INFERTILITY TREATMENT Jabez C. Gondokusumo, J. Abram McBride, Daniel J. Mazur, and Larry I. Lipshultz Jabez C. GondokusumoJabez C. Gondokusumo More articles by this author , J. Abram McBrideJ. Abram McBride More articles by this author , Daniel J. MazurDaniel J. Mazur More articles by this author , and Larry I. LipshultzLarry I. Lipshultz More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.3074AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Follicle-stimulating hormone (FSH) is a gonadotropin produced by the anterior pituitary gland and is trophic to the sertoli cells to maintain spermatogenesis. FSH is prescribed to men with hypogonadotropic hypogonadism (congenital or acquired) seeking fertility. Commercially available FSH, branded Gonal-F (B-FSH), is often cost prohibitive for patients, leading to the recent development of compounded alternatives. Here we compare the clinical and cost-effectiveness of B-FSH with compounded FSH (C-FSH). METHODS We retrospectively reviewed patient records from a high-volume andrology clinic for those who were prescribed C-FSH treatment for azo/severe oligozoospermia and undetectable FSH levels. All C-FSH prescriptions were sent through Empower Pharmacy in Houston, Texas. We assessed the patients initial FSH level, post-treatment FSH level, reason for seeking treatment, and follow up of treatment success, if available. In addition, the cost of B-FSH across 9 major commercial pharmacies was obtained through goodrx.com for comparison to C-FSH. RESULTS 17 patients were prescribed C-FSH, of which 11 showed statistically significant increases in baseline FSH levels (p-value = 0.003). However, patient compliance with medication administration in those not showing FSH improvement is unknown due to incomplete records. Of the 11 C-FSH responders, 5 of them were able to achieve pregnancy and live birth of healthy children, 2 with intrauterine insemination (IUI) and 3 with in-vitro fertilization (IVF). Of the remaining 6 C-FSH responders, 2 underwent unsuccessful attempts at IVF, but female factors were also present. The fertility status of the remaining 4 C-FSH responders was not known from chart review. Of importance, the average total price per unit for B-FSH across commercial pharmacies was found to be $2.20 per unit compared to $0.20 per unit of C-FSH from Empower Pharmacy. CONCLUSIONS All the patients with complete records exhibited FSH levels in the normal range after treatment with C-FSH. Realizing that the starting dose of FSH for hypogonadotropic hypogonadism is 75-150 units three times weekly until therapeutic goals are achieved (months to years), the tremendous cost saving with C-FSH is without question. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e92 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Jabez C. Gondokusumo More articles by this author J. Abram McBride More articles by this author Daniel J. Mazur More articles by this author Larry I. Lipshultz More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Oocyte cryopreservation for women with GATA2 deficiency.

To describe controlled ovarian stimulation (COS) in a population of women with GATA2 deficiency, a genetic bone marrow failure syndrome, prior to allogeneic hematopoietic stem cell transplant METHODS: This is a retrospective case series of nine women with GATA2 deficiency who underwent oocyte preservation at a research institution. Main outcomes measured include baseline fertility characteristics ((antimullerian hormone (AMH) and day 3 follicle-stimulating hormone (FSH) and estradiol (E2)) and total doses of FSH and human menopausal gonadotropins (HMG), E2 on day of trigger, and total number of metaphase II oocytes retrieved. The mean age was 24years [16-32], mean AMH was 5.2ng/mL [0.7-10], and day 3 mean FSH was 5.1U/L [0.7-8.1], and E2 was 31.5pg/mL [< 5-45]. The mean dose of FSH was 1774IU [675-4035], and HMG was 1412IU [375-2925] with a mean E2 of 2267pg/mL [60.7-4030] on day of trigger. The mean total of metaphase II oocytes was 7.7 [0-15]. One patient was diagnosed with a deep vein thrombosis (DVT) with pulmonary embolism (PE) during COS. This study is the first to analyze the outcomes of COS in women with GATA2 deficiency. The response to ovarian stimulation suggests that oocyte cryopreservation should be considered prior to gonadotoxic therapy. However, due to the risk of potentially life-threatening complications, it is prudent that patients are properly counseled of the risks and are evaluated by a multi-disciplinary medical team prior to COS.

Follicle-stimulating hormone enhances hepatic gluconeogenesis by GRK2-mediated AMPK hyperphosphorylation at Ser485 in mice.

Increased serum follicle-stimulating hormone (FSH) is correlated with fasting hyperglycaemia. However, the underlying mechanism remains unclear. Because excessive hepatic gluconeogenesis is a major cause of fasting hyperglycaemia the present study investigated whether FSH increases hepatic gluconeogenesis in mice. Ovariectomised mice supplemented with oestradiol (E2) to maintain normal levels of serum E2 (OVX+E2 mice) were injected with low or high doses of FSH. We knocked out Crtc2, a crucial factor in gluconeogenesis, and Fshr to discern their involvement in FSH signalling. To evaluate the role of the G-protein-coupled receptor (GPCR) kinase 2 (GRK2), which could affect glucose metabolism and interact directly with non-GPCR components, a specific GRK2 inhibitor was used. The pyruvate tolerance test (PTT), quantification of PEPCK and glucose-6-phosphatase (G6Pase), key enzymes of gluconeogenesis, GRK2 and phosphorylation of AMP-activated protein kinase (AMPK) were examined to evaluate the level of gluconeogenesis in the liver. A nonphosphorylatable mutant of AMPK Ser485 (AMPK S485A) was transfected into HepG2 cells to evaluate the role of AMPK Ser485 phosphorylation. FSH increased fasting glucose (OVX+E2+high-dose FSH 8.18 ± 0.60mmol/l vs OVX+E2 6.23 ± 1.33mmol/l), the PTT results, and the transcription of Pepck (also known as Pck1; 2.0-fold increase) and G6pase (also known as G6pc; 2.5-fold increase) in OVX+E2 mice. FSH also enhanced the promoter luciferase activities of the two enzymes in HepG2 cells. FSH promoted the membrane translocation of GRK2, which is associated with increased AMPK Ser485 and decreased AMPK Thr172 phosphorylation, and enhanced the nuclear translocation of cyclic AMP-regulated transcriptional coactivator 2 (CRTC2). GRK2 could bind with AMPK and induce Ser485 hyperphosphorylation. Furthermore, either the GRK2 inhibitor or AMPK S485A blocked FSH-regulated AMPK Thr172 dephosphorylation and gluconeogenesis. Additionally, the deletion of Crtc2 or Fshr abolished the function of FSH in OVX+E2 mice. The results indicate that FSH enhances CRTC2-mediated gluconeogenesis dependent on AMPK Ser485 phosphorylation via GRK2 in the liver, suggesting an essential role of FSH in the pathogenesis of fasting hyperglycaemia.

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Individualised gonadotropin dose selection using markers of ovarian reserve for women undergoing in vitro fertilisation plus intracytoplasmic sperm injection (IVF/ICSI).

Ovarian response after random-start controlled ovarian stimulation to cryopreserve oocytes in cancer patients.

ObjectiveTo evaluate COS and oocyte retrieval results in ART treatment cycles initiated at any stage of the menstrual cycle (random start) in cancer patients, who could not postpone the onset of cancer treatment.MethodsProspective observational study of 26 women with cancer, with an indication to start cancer treatment within the next 20 days and wishing to preserve their fertility. Ovarian stimulation started immediately with FSH followed by GnRH antagonist for pituitary suppression and GnRH agonist for oocyte maturation. Treatment started from day 1 to day 14 of the menstrual cycle was considered to be in the follicular phase, and that started from day 15 to day 28 was considered to be in the luteal phase. Oocyte retrieval was performed 34 h after GnRH agonist administration. After identification and maturity classification, metaphase II oocytes were cryopreserved using vitrification.ResultsA total of 13 women had breast cancer, 4 ovarian cancer, 3 Central Nervous System cancer, 3 endometrial cancer, 2 cervical cancer and one bowel cancer. Thirteen patients started treatment during follicular phase and 13 during luteal phase. We found similar results for the duration of treatment, total dose of follicle stimulating hormone, number of ampoules of gonadotropin releasing hormone antagonist, mean number of follicles identified at ultrasound on the day of trigger and retrieval, number of aspirated oocytes and Metaphase II oocytes.ConclusionRandom-start controlled ovarian stimulation for emergency fertility preservation for minimizing delay in oncologic treatment for cancer patients does not interfere with the number of metaphase II oocytes, and therefore can be routinely used for stimulation followed by cryopreservation.

Follicular response and oocyte production following variations in ovarian stimulation in goats

In this study, goats were subjected to ovarian stimulation protocols to evaluate possible differences in ovarian follicular responses and oocyte production. Two experiments were conducted to assess the effects of hormonal protocol duration (seven or twelve days) and number of follicle stimulating hormone (FSH) applications (one or five doses). All animals received intravaginal sponges saturated with 60 mg medroxyprogesterone acetate and an application of 125 μg cloprostenol 72 h before the sponges were removed. For ovarian stimulation, 120 mg FSH was applied in a single dose 36 h before laparoscopic follicular aspiration (LOPU) or in five doses (30, 30, 20, 20, and 20 mg) at 12 h intervals, with the last dose applied 36 h before LOPU. In the first experimental phase, ultrasonography was performed to monitor follicular number and diameter, and in the second phase, the animals received LOPU to count the follicles and cumulus-oocyte complexes (COCs) and for morphological classification. There was no significant effect (P > 0.05) of any variable or combination of variables on follicle number on Day (D) 0 or D3/D8 (day of LOPU). However, evaluation at D6/D11 revealed an effect (P < 0.05) from the protocol duration with the highest number of small follicles resulting from the short protocol. There was also an effect (P < 0.05) of FSH dose number on the resulting number of medium and large follicles, with more medium follicles recovered after a single dose and more large follicles after multiple doses. There was no effect of any variable (P > 0.05) on the diameters of the large, medium, and small follicles, except for the D4/D9 evaluation, which showed a combination effect for large follicles (P < 0.05). In the second phase, no variable had an effect on the number of follicles visualized or aspirated, number of COCs recovered, recovery rate, morphological quality of COCs in grades 1, 2, 3, and 4, or rate of viable COCs. Thus, all four protocols efficiently stimulated the ovarian response and oocyte production of goats, although the short protocol (7 days) with a single dose of FSH was most efficacious based upon the greater number of medium-sized follicles available for aspiration, the shorter time, and greater practicality of execution.

Expression of FSHR in chondrocytes and the effect of FSH on chondrocytes

ObjectiveChondrocytes express many kinds of hormone receptors. The function of Follicle stimulating hormone (FSH) in the ovary is mediated by FSH receptor (FSHR). FSH receptor (FSHR) is found in many non-ovarian tissues, however it has been unclear if chondrocytes express FSHR. The purpose of this study is to determine it. MethodsMouse primary chondrocytes and human articular cartilage tissues were examined. The expression and sequence of FSHR mRNA by reverse transcription polymerase chain reaction (RT-PCR) and sequenced, respectively, and its protein expression was tested using western blotting and location was observed under immunofluorescence microscopy. Ovarian tissue was as a positive control. After FSH stimulated mouse chondrocytes, intracellular cAMP levels were assessed by ELISA, and gene expression relative to Mouse WNT Signaling Pathway was tested by RT2 Profiler PCR Arrays. ResultsFSHR was detected at the transcriptional level and confirmed to have the same sequence as that of ovary-derived mRNA of FSHR. FSHR proteins presented at the same line as the positive proteins of ovary, in mouse chondrocytes and human cartilage tissue, respectively. FSHR proteins were located at the cell membrane. Intracellular cAMP contents were significantly elevated up to 7-fold in mouse chondrocytes by forskolin (100 mM) (P < 0.001); however, different doses of FSH did not change the cAMP contents in mouse primary chondrocytes. RT2 Profiler PCR Arrays demonstrated that FSH could cause changes in gene expression among the 84 preordained genes, such as Fosl1, Rhou, and Dkk1, in mouse chondrocytes relative to the control. ConclusionMouse chondrocytes and human articular cartilage express functional FSHR. Moreover, FSH can act on chondrocytes and cause genetic changes.

Bemfola® fixed dose pens potentially reduce drug wastage and associated costs of infertility treatment

Bemfola® is a recombinant follicle-stimulating hormone (FSH) used during infertility treatment. One main differentiator between FSH products is their delivery device; consisting of multi-dose pens (Gonal-f®), vials or multi-dose preparations (Menopur®), or adjustable daily disposable dose pens (Bemfola®). To determine the potential impact of delivery device on drug wastage during infertility treatment this study retrospectively analysed Gonal-f® and Menopur® prescription and usage data from five UK clinics. Incurred drug wastage was then compared to potential Bemfola® drug wastage. Data collected included: (i) number of treatment cycles; (ii) daily FSH dose; (iii) length of treatment; (iv) dose adjustment following ultrasound scan; (v) FSH formulation(s) prescribed and (vi) agonist/antagonist protocol used. Treatment with Gonal-f® (4078 cycles) and Menopur® (646 cycles) resulted in an average drug wastage of 160 and 294 IU per treatment cycle. Use of Bemfola® instead of Gonal-f® and Menopur® may reduce the wastage to 104 and 61 IU per cycle, respectively. The use of Bemfola®, across all 4724 cycles, could result in a drug wastage reduction of up to 376,800 IUs with an associated cost saving of £100,011. Bemfola® is a viable alternative to Gonal-f® and Menopur® with its drug delivery system potentially reducing drug wastage and associated costs during infertility treatment.

Effect of different doses of FSH on superovulation, productionand quality of embryo in North Omani Cattle breed

The experiment was conducted to investigate the Ovarian response and embryo quality using different doses of follicle stimulating hormone (FSH-P) in North Omani Cattle breed (NOC) in order to determine the suitable dose. Eighteen donor NOC were divided into three groups (G1, G2, and G3) comprising of six cows in each group and treated with 20 (G1), 25 (G2) and 30 mg FSH (G3). Ovarian response was recorded as development of corpus luteum (CL), unovulated follicles (UOF), unfertilized ova (UFO), recovered embryo (RE) and transferable embryos (TE). Embryos were flushed seven days after the first AI and classified according to the developmental stage and quality. Results showed that, cows superovulated with FSH (G3) increased significantly (P less than 0.05) number of CLs and number of RE (6.83 and 5.33 /flushed cow) compared with the G1 of FSH (3.17 and 2.00/flushed cow) and G2 (4.67 and 3.00/flushed cow). While using FSH in (G2) increased significantly (P less than 0.05) the number of TE (excellent and good) quality, decreased average number of UOF and UFO (2.84, 3.33 and 0.67/flush) compared with FSH G3 (1.83, 5.67 and 1.50/flush). While no significant difference was observed in TE number between G1 and G2. G3 groups producing embryos at early stages of development (4 and 8 cells) and this was undesirable for embryo transfer program as this treatment (30 mg) produced more number of fair, poor and degenerated embryos compared with 20 and 25 mg FSH. Consequently, 25 mg FSH dose increased number of TE, decreased number of UOF and UFO, and that was the suitable dose for superovulation of NOC.