366 THE BOVINE MODEL FOR REPRODUCTIVE AGING: SUPEROVULATORY RESPONSE

2006 ◽  
Vol 18 (2) ◽  
pp. 290
Author(s):  
P. S. Malhi ◽  
G. P. Adams ◽  
R. J. Mapletoft ◽  
J. Singh
Keyword(s):  
Body Weight ◽  
Animal Health ◽  
Ovarian Response ◽  
Reproductive Aging ◽  
Ultrasound Guided ◽  
Expected Time ◽  
Follicular Wave ◽  
Follicular Aspiration ◽  
The Difference ◽  
Follicular Response

Two experiments were done to test the hypotheses that aging in cattle is associated with a reduction in the number of follicles recruited into an ovarian follicular wave, and a reduction in the ovarian response following gonadotropin treatment for superovulation. Old cows (13 to 16 years old; n = 6 to 9) and their young daughters (3 to 6 years old; n = 7 to 9) were treated to induce an ovarian superstimulatory response twice in each of two consecutive years (i.e. 31 and 33 superstimulatory cycles, respectively). In Experiment 1, follicular wave emergence was synchronized using a single treatment of estradiol (5 mg) combined with progesterone (100 mg) at the time of CIDR-B (Bioniche Animal Health, Belleville, Ontario, Canada) insertion. Superstimulatory treatment consisted of a total dose of 50 mg NIH-FSH-P1 (Folltropin-V; Bioniche Animal Health) per 100 kg body weight divided into twice daily intramuscular injections over 4 days. CIDR devices were removed at the time of the last FSH treatment and 500 �g cloprostenol (Estrumate; Schering-Plough Animal Health, Montreal, Quebec, Canada) was administered twice along with last two FSH treatments to induce luteolysis. Ovulation was induced using 25 mg porcine LH (Lutropin-V; Bioniche Animal Health) administered 24 h after the last FSH treatment. Ovulations were detected by ultrasonography at 24, 48, and 72 h after LH treatment. In Experiment 2, follicular wave emergence was synchronized with ultrasound-guided follicle ablation in the presence of a functional corpus luteum. Superstimulatory treatment was given as in Experiment 1. Ultrasound-guided follicle aspirations were performed 48 to 72 h after the last FSH for the purpose of another experiment. In both experiments, the ovarian follicular response was monitored daily by ultrasonography. There were no differences (P > 0.3) in mean body weight and dose of FSH treatment between old cows and their daughters. Fewer 2-5-mm follicles (P < 0.01) were detected at the expected time of wave emergence in old cows than in their daughters. In Experiment 1, the difference in mean number of ovulations in old and young cows (32 � 4 vs. 40 � 3) did not reach significance (P = 0.11), but fewer follicles e6 mm (P < 0.01) were detected on the day before ovulation in old cows than in their daughters. The number of follicles e6 mm detected just before ovulation (Experiment 1) or follicular aspiration (Experiment 2) in successive superstimulatory cycles was correlated within animals (r > 0.8; P < 0.0001). Similarly, the number of ovulations in successive superstimulatory cycles (Experiment 1) was correlated within animals (r = 0.6; P = 0.04). In conclusion, aging was associated with fewer 2-1 mm follicles at the time of wave emergence, a lower follicular response, and a tendency for a lower ovulatory response subsequent to gonadotropin treatment. The follicular and ovulatory response to superstimulatory treatment was repeatable within individuals.

263 IN VITRO FERTILIZATION AND EMBRYO DEVELOPMENT OF CUMULUS - OOCYTE COMPLEXES COLLECTED BY ULTRASOUND-GUIDED FOLLICULAR ASPIRATION IN LLAMAS TREATED WITH GONADOTROPIN

2010 ◽  
Vol 22 (1) ◽  
pp. 288 ◽  
Author(s):  
M. A. Berland ◽  
A. von Baer ◽  
V. Parraguez ◽  
P. Morales ◽  
G. P. Adams ◽  
...  
Keyword(s):  
In Vitro Fertilization ◽  
Embryo Development ◽  
Animal Health ◽  
Ovarian Response ◽  
Ultrasound Guided ◽  
Vitro Fertilization ◽  
Follicular Aspiration ◽  
Oocyte Collection ◽  
Health Canada

We have previously documented that both FSH and eCG are equally effective in inducing ovarian superstimulation in llamas, resulting in the recovery of a high number of expanded COC suitable for in vitro fertilization (Ratto et al. 2005 Theriogenology 63, 2445-2457). The objective of the study was to evaluate the ovarian response, morphology, and competence of COC collected by ultrasound-guided follicular aspiration in llamas treated with FSH or eCG. Llamas were assigned randomly into 2 groups (n = 16 per group) and treated for 48 h after follicle ablation with (1)25 mg of FSH (Folltropin, Bioniche Animal Health Canada Inc., Belleville, Canada) i.m. twice daily for 4 d; or (2) 1000IU of eCG (Novormon, Bioniche Animal Health Canada) as a single i.m. dose. The starting of gonadotropin treatment was considered Day 0. Both groups were given an i.m. dose of 5 mg of Armour Standard LH (Lutropin, Bioniche Animal Health Canada) on Day 6, and COC were collected by transvaginal ultrasound follicle aspiration of all follicles ≥7 mm on Day 7. The ovarian response was assessed by transrectal ultrasonography using a 7.5-MHz linear-array transducer (Aloka SSD-500, Clinics, Santiago, Chile) immediately before oocyte collection at 24 to 26 h after LH treatment in both groups. The COC were classified as expanded, compact, denuded, or degenerated. Expanded COC collected from FSH- (n = 147) and eCG-treated llamas (n = 141) were fertilized in vitro using epididymal sperm as previously described (Ratto et al. 2006 Anim. Reprod. Sci. 97, 246-257). Gametes were co-incubated at 38.5°C in air with 5% CO2 and high humidity for 18 h. After in vitro fertilization, presumptive zygotes were co-culture in SOF medium supplemented with 0.6% of BSA with llama granulosa cells at 39°C, 5% CO2, 5% O2, and 90% N2 for 7 days. Embryo development was evaluated on Days 2, 5, and 7 of in vitro culture (Day 0 = IVF). Data were analyzed by Student’s t-test or Fisher’s exact test and presented as mean ± SEM. The FSH and eCG treatment groups did not differ with respect to the number of follicles ≥7 mm at the time of COC collection (16.0 ± 2.7 v. 14.0 ± 1.9; P = 0.5), the number of COC collected (11.5 ± 1.9 v. 9.7 ± 1.2; P = 0.4), or the collection rate per follicle aspirated (77.0 v. 71.5%; P = 0.2). No difference was detected between FSH and eCG-treated llamas in the number of expanded COCs (9.8 ± 1.4 v. 9.4 ± 1.2; P = 0.8). The percentage of presumptive zygotes to develop into 2 to 8 cells on Day 2 (65.3 v. 63.1), morulas on Day 5 (46.2 v. 42.5), and blastocyst stage on Day 7 (23.1 v. 20.5) did not differ (P > 0.05) between FSH and eCG-treated llamas, respectively. In conclusion, FSH and eCG treatments were equally effective for ovarian superstimulation and oocyte collection. The recovery of a high number of expanded COC can be used directly for in vitro fertilization and their competence is not affected by gonadotropin treatment. The study was supported by Convenio Desempeño en Investigacion (2007-DGI-CDA-04), Universidad Catolica de Temuco.

295 SUPEROVULATORY RESPONSE IN COWS FOLLOWING SYNCHRONIZATION OF FOLLICLE WAVE EMERGENCE WITH ESTRADIOL AT DIFFERENT STAGES OF THE ESTROUS CYCLE

2008 ◽  
Vol 20 (1) ◽  
pp. 227
Author(s):  
A. Garcia Guerra ◽  
G. A. Bó ◽  
J. Villarreal ◽  
G. M. Brogliatti
Keyword(s):  
Estrous Cycle ◽  
Buenos Aires ◽  
Animal Health ◽  
Ovarian Response ◽  
Buenos Aires Province ◽  
Transfer Program ◽  
Dominant Follicle ◽  
Follicular Wave ◽  
Significant Difference ◽  
Group 2

Ovarian asynchrony and variability in response to superstimulation remain the most limiting factors in any embryo transfer program (Armstrong D 1993 Theriogenology 39, 7–24). Ovarian response can be increased and less variable if superstimulatory treatment is started at the time of follicular wave emergence (Bö GA et al. 1995 Theriogenology 43, 31–40). A combination of progesterone (P4) and estradiol have been used to synchronize follicular wave for superstimulation. A retrospective analysis was done to compare the ovarian response, superovulatory response and embryo production of cows in Argentina that received progesterone and estradol prior to superstimulation at different stages of the estrous cycle. This research was carried out using different breed of donors (n = 584, 88% Angus) during the last 4 years in Buenos Aires province, Argentina. Heat detection was performed twice a day. At random stages of the estrous cycle, donors received an intravaginal progesterone device (DIB; Syntex, Buenos Aires, Argentina), 2 mg of estradiol benzoate and 50 mg of progesterone (Syntex, Buenos Aires, Argentina) IM on the same day. On day 4 after DIB insertion, superestimulatory treatment was initiated on a decreasing dose regimen of FSH (Pluset; Callier, Spain, or Folltropin, Bioniche Animal Health Inc., Belleville, Ontario, Canada) as IM injections every 12 h over 4 d. On day 6, DIBs were removed, and cows received two doses of 2 mL of cloprostenol 12 h apart. At heat detection, all donors received a dose of 2 mL of GnRH (Dalmarelin; Fatro Von Franken, Buenos Aires, Argentina) by IM injection and were inseminated 12 and 24 h later. Seven days later, embryo collection was performed and ovarian response was evaluated as number of CL + unovulated follicles by transrectal ultrasound using a 7.5-MHz transducer (Pie Medical, Maastricht, the Netherlands). Ova/embryos were evaluated and classified according to the IETS manual. Donors were assigned to receive DIB and estradiol during the following stages of the cycle: group 1: between days 4 and 7 post-estrus (dominant follicle period), group 2: between days 8 and 12 post-estrus (emergence of the second follicular wave), and group 3: between days 13 and 21 post-estrus (dominant follicle of the second wave). Kruskal-Wallis test was used to compare variables among groups, and results are shown in Table 1. Ovarian response as CL + unovulated follicles and number of ovulations were significantly different among groups (P < 0.05). However, there was no significant difference in the number of fertilized ova or transferable embryos. Nevertheless, numeric differences that show that group 2 (started between days 8 and 12 post-estrus) was always superior for all variables. In conclusion, data suggest that estradiol may be more effective in synchronizing follicle wave emergence for superstimulation during the mid-part of the estrous cycle. Table 1. Superovulatory response in cows in which follicle wave emergence was synchronized with estradiol at different stages of the estrous cycle (mean ± SD) Research supported by Centro Genetico Bovino Eolia S.A.

202 ANTRAL FOLLICULAR COUNTS AND SUPERSTIMULATORY RESPONSE IN PREPUBERTAL CALVES

2017 ◽  
Vol 29 (1) ◽  
pp. 210
Author(s):  
A. R. T. Krause ◽  
F. C. F. Dias ◽  
G. Adams ◽  
R. Mapletoft ◽  
W. F. Huanca ◽  
...  
Keyword(s):  
Natural Science ◽  
Animal Health ◽  
Transrectal Ultrasound ◽  
Correlation Coefficients ◽  
Ovarian Response ◽  
Science And Engineering ◽  
Follicular Wave ◽  
Video Recordings ◽  
Oocyte Collection ◽  
Science Without Borders

The number of follicles recruited in successive waves are consistent in postpubertal cattle (Singh et al. 2004 Theriogenology 62, 227), but ovarian response to gonadotropin stimulation is highly variable among animals. We tested the hypotheses that the number of follicles present at wave emergence are repeatable and are predictive of superstimulatory response in prepubertal calves; therefore, we expected that calves with higher antral follicular counts (AFC; follicles = 1mm) at wave emergence will result in a greater number of follicles available for oocyte collection after a conventional 4-day gonadotropin treatment. Hereford crossbreed calves (n = 52; 5.1 to 6.8 months of age) were ranked according to the number of follicles = 1 mm detected in transrectal ultrasound video recordings of both ovaries at the time of wave emergence (First AFC; range: 12 to 53 follicles). Calves in the bottom (Low AFC; <20 follicles; n = 6) and top (High AFC; >32 follicles; n = 5) quartiles were selected for ovarian superstimulation. Emergence of a new follicular wave (Day 0) was induced by transvaginal follicle ablation (14 to 57 days after first AFC; 5.7 to 7.1 months of age), AFC were performed again (Second AFC), and calves were given eight 12-hourly IM injections of 25 mg of pFSH (Folltropin-V®, Bioniche Animal Health Inc., Belleville, Canada) beginning on Day 0.5. All calves were given 12.5 mg of pLH (Lutropin-V®, Bioniche Animal Health Inc.) IM 12 h after the last FSH and number of follicles equal to 3, 3 to 5, 6 to 8, and equal to 6 and 9 were counted 24 h after LH treatment (at the time of oocyte collection). A t-test was used to compare the number of follicles and ovarian response (Low v. High AFC). Values of Pearson (0.8; P < 0.001) and Spearman (0.9; P < 0.001) correlation coefficients between First and Second AFC indicate strong repeatability of numbers of follicles present at the time of wave emergence. As expected, mean number of follicles were greater (P = 0.01) in the High- than Low-AFC group (24.2 ± 2.0 v. 15.7 ± 1.0) at the Second AFC. The High-AFC group had a greater number of follicles at oocyte collection than Low AFC for 6 to 8 mm (13.4 ± 2.1 v. 5.3 ± 1.7; P = 0.01), but not for 3 to 5 mm (9.4 ± 2.5 v. 5.3 ± 2.1; P = 0.2) or 9 mm (7.6 ± 2.9 v. 4.8 ± 2.0; P = 0.4) size categories. However, High AFC resulted in a greater total number of follicles 3 (30.4 ± 3.1 v. 15.5 ± 3.2; P = 0.009) and 6 mm (21.0 ± 4.1 v. 10.2 ± 2.9; P = 0.05). The number of 6-mm follicles at the end of superstimulation represented 80 and 60% of 1-mm follicles at wave emergence in the High- and Low-AFC groups (P = 0.3). In conclusion, the number of follicles at the beginning of a wave are predictive of follicles recruited into subsequent waves in 7-month-old calves, and higher AFC at wave emergence resulted in a greater number of 3- and 6-mm follicles available for oocyte collection. Research was supported by the Natural Science and Engineering Council of Canada (NSERC). Hormones provided by Vetoquinol Inc. ARTK funded by CNPq-Science Without Borders, Brazil.

27 FOLLICULAR RESPONSE TO DIFFERENT eCG DOSES IN AN OVSYNCH + PROGESTERONE PROTOCOL IN BEEF HEIFERS

2010 ◽  
Vol 22 (1) ◽  
pp. 171
Author(s):  
M. F. Martínez ◽  
D. Tutt ◽  
L. Proctor ◽  
J. L. Juengel
Keyword(s):  
New Zealand ◽  
Animal Health ◽  
Follicular Development ◽  
Dominant Follicle ◽  
Treatment Groups ◽  
Follicular Wave ◽  
Multiple Ovulation ◽  
Array Transducer ◽  
Pfizer Animal Health ◽  
Follicular Response

An experiment was designed to evaluate the effect of different doses of eCG on ovarian follicular dynamics in heifers treated with a Ovsynch plus progesterone protocol. Twenty-five cyclic yearling Black Angus heifers (373.0 ± 35.7 kg), in 2 replicates, received an injection of 100 μg of GnRH (Ovurelin, Bomac Laboratories Ltd., Auckland, New Zealand) i.m. and an intravaginal progesterone device (1.38 g of progesterone; Eazi-Breed CIDR, Pfizer Animal Health, New Zealand) on Day 0 (beginning of the experiment), followed by 500 μg of cloprostenol (PGF, Estrumate, Intervet/Schering-Plough Animal Health, Auckland, New Zealand) i.m. on Day 7, and a second 100 μg of GnRH injection given i.m. on Day 9 (56 h after PGF). At the time of PGF treatment, heifers were randomly assigned to 5 treatment groups to receive 0, 300, 500, 700, or 1000 IU of eCG (Folligon, Intervet/Schering-Plough Animal Health) i.m. Heifers were monitored by ultrasonography (Aloka 900-SSD equipped with a 7.5-MHz linear-array transducer; Aloka, Tokyo, Japan) daily from Day 0 to 9 (GnRH), and then every 12 h until ovulation. Data were analyzed by one-way ANOVA or Kruskall-Wallis test, and means or ranks were compared with LSD or Wilcoxon rank sum tests, respectively. Because a replicate effect was observed (P < 0.05) in the size of the dominant follicle at the second GnRH and prior to ovulation, replicate effect was included in the analysis. The luteal area at PGF treatment was significantly greater (P < 0.01) in heifers that ovulated (750.0 ± 97 mm2) in response to the first GnRH treatment than in those that did not (301.6 ± 42.7 mm2). The diameter of the dominant follicle at the time of PGF treatment was also greater (P < 0.05) in ovulating (11.2 ± 0.4 mm) than in nonovulating (9.7 ± 0.5 mm) heifers. The interval from the first GnRH treatment to the emergence of the next follicular wave was longer (P = 0.50) and more variable in heifers that did not ovulate (2.9 ± 0.4 d; n = 27) than in those that ovulated (1.9 ± 0.2 d; n = 23). There was no effect (P < 0.37) of eCG on the interval from PGF to ovulation (86 ± 1.9 h). The number of ovulations after the second GnRH was higher (P = 0.01) in the group of heifers treated with 1000 IU of eCG (1.8 ± 0.4) than in the other groups (1.0 ± 0.0; 1.1 ± 0.1; 1.2 ± 0.1; 1.0 ± 0.1). There was an effect of day of follicular wave emergence on the number of ovulations (P < 0.01). Heifers with a wave emerging 1 to 3 days after the first GnRH (n = 37), had one ovulation (1.0 ± 0.0), whereas heifers with a wave emerging on Day 4 (3 out of 4 heifers) and Days 5 to 7 (n = 9), ovulated 2 or more follicles. In summary, the multiple ovulation effect occurred when eCG was given to heifers with a follicular wave emerging on or after Day 4, and was potentiated when heifers received 1000 IU of eCG. Although the dose of eCG given at the time of PGF treatment in an Ovsynch program has a significant effect on follicular development, the time of emergence of the dominant follicle appeared to be more important in the ovulation of preovulatory follicle/s after the eCG and the second GnRH treatment.

123 Efficiency of embryo production using ovum pickup oocytes recovered from stimulated and nonstimulated cows

2021 ◽  
Vol 33 (2) ◽  
pp. 169
Author(s):  
R. Y. Chinarov ◽  
G. N. Singina ◽  
V. Havlicek ◽  
N. P. Taradajnic ◽  
T. E. Taradajnic ◽  
...  
Keyword(s):  
Animal Health ◽  
Calf Serum ◽  
Prostaglandin F2α ◽  
Essential Element ◽  
Developmental Competence ◽  
Ultrasound Guided ◽  
Russian Science ◽  
Hormonal Stimulation ◽  
Follicular Aspiration ◽  
Significant Difference

Recovery of oocytes from live animals through ultrasound-guided transvaginal follicular aspiration (ovum pickup, OPU) is an essential element of modern livestock development. To increase the number of OPU oocytes retrieved, hormonal stimulation is broadly applied; however, the results are ambiguous. The aim of the present study was to compare recovery rate, quality of oocytes, and efficiency of invitro production of cattle embryos using OPU oocytes derived from hormonal treated and untreated cows. The study was performed in Simmental heifers at the age of 17 to 23 months. The heifers in the first group (n=7) were previously synchronized using prostaglandin F2α (Estrumate, MSD Animal Health) and gonadotrophin-releasing hormone (GnRH; Receptal, MSD Animal Health) and then underwent superstimulation with Stimofol (Reprobiol SPRL, Belgium) in a total amount of 0.25mg of FSH and 0.05mg of LH in a treatment of 6 injections on 3 consecutive days starting on Day −4 before OPU. The heifers of the second group (n=2) underwent OPU once a week for 5 weeks (10 OPU sessions). Groups of recovered cumulus–oocyte complexes (COCs) were matured in TCM-199 containing 10% fetal calf serum, 1mM Na-pyruvate, 50μg mL−1 gentamycin, 10μg mL−1 FSH, and 10μg mL−1 LH for 24h, fertilized in Fert-TALP (Tyrode’s-albumin-lactate-pyruvate) for 18 to 20h, and cultured in CR1aa medium for 7 days. All steps of IVP were performed at 38.5°C with 5% CO2 and 90% humidity. The cleavage and blastocysts rates were assessed on Day 2 and 7, respectively. In addition, Day-7 blastocysts were fixed, and the total cell number was determined using 4′,6-diamidino-2-phenylindole (DAPI) staining. The data were analysed by ANOVA using SigmaStat software package. As expected, the number of aspirated follicles per session in the first group of cows was higher than that in the second group: 14.6±1.2 vs. 6.8±0.5 (P&lt;0.05). In total, 54 and 42 COCs were collected, which corresponds to recovery rates of 54.5±7.7 and 61.3±4.9% for stimulated and nonstimulated cows, respectively. After the quality evaluation, 36 COCs of SS heifers (67.2±1.9%) and 31 COCs of non-SS heifers (75.3±5.0%) were selected for IVP. We did not observe a significant difference in cleavage rate between two groups: 77.8% in the SS group vs. 71.0% in the non-SS group, whereas the rate of blastocyst production was higher (P&lt;0.05) for SS heifers (25.0%) compared with non-SS animals (16.1%). The total number of cells in Day 7 blastocysts was significantly (P&lt;0.01) higher in the first group (89.8±1.3) compared with the second group (70.6±3.2). Thus, superstimulation of heifers before OPU increases the efficiency of oocyte retrieval by ultrasound-guided transvaginal follicular aspiration as well as the developmental competence of OPU-derived bovine oocytes invitro. These studies were performed under financial support of the Russian Science Foundation (project No. 19-16-00115) and the Ministry of Science and Higher Education of Russia.

Seasonal variations in wool growth and heat tolerance of sheep. I. Wool growth

1960 ◽  
Vol 11 (1) ◽  
pp. 75 ◽  
Author(s):  
M Wodzicka
Keyword(s):  
Body Weight ◽  
Day Treatment ◽  
The Other ◽  
Seasonal Rhythm ◽  
Group Iii ◽  
Wool Growth ◽  
Group I ◽  
The Mean ◽  
Group Ii ◽  
The Difference

The monthly wool growth of three groups of rams was studied at Beltsville, Maryland. Group I received natural daylight (at 38° 53' N.) and was shorn monthly. Group II had a 7:17 hours of daylight to hours of darkness rhythm and was shorn every 6 months, once in winter and once in summer. Group III received natural daylight and was likewise shorn every 6 months. The rams of all groups produced more wool in summer than in winter. This difference was significant (P<0.001). The mean body weight and food intake were both greater in the winter months, which indicated that the seasonal rhythm of wool growth was not a consequence of poorer feeding in winter. The rams which were shorn monthly (group I) grew considerably more wool than the other two groups, but the difference was not statistically significant. The short-day treatment of group II did not increase the annual wool production nor decrease the seasonal rhythm of wool growth. The balance of evidence from this and other experiments indicates that temperature rather than light controls the seasonal rhythm of wool growth.

P–650 Body weight is the main determinant of systemic follicle stimulating hormone (FSH) concentrations during controlled ovarian stimulation with follitropin delta

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
D Jonker
Keyword(s):  
Renal Function ◽  
Body Weight ◽  
Black Women ◽  
Ovarian Stimulation ◽  
Ovarian Response ◽  
Hepatic Function ◽  
Controlled Ovarian Stimulation ◽  
Confidence Limits ◽  
Main Determinant ◽  
Asian Race

Abstract Study question Which individual subject characteristics affect systemic FSH concentrations in women undergoing controlled ovarian stimulation with follitropin delta? Summary answer Body weight is the main determinant of systemic FSH concentrations. Renal function, Asian race, country/region, hepatic function and age have at most a small influence. What is known already After administration of FSH, systemic FSH concentrations are inversely related to body weight. It has been observed that the impact of body weight on ovarian response is clinically relevant at low doses but not at high doses. In patients with anti-Müllerian hormone (AMH) ≥15 pmol/L, follitropin delta is dosed according to each patient’s body weight, which influences systemic FSH concentrations, and her AMH level which predicts ovarian response. Study design, size, duration Serum FSH concentrations were assessed in five randomised, controlled, assessor-blinded, multicentre trials of follitropin delta in women undergoing an assisted reproductive technology programme. The trials were conducted in Europe, America and Asia. In all, 1.665 women treated with follitropin delta contributed to the evaluation with 4052 serum FSH concentrations, measured at steady state by an immunoassay. Participants/materials, setting, methods FSH concentrations were described with a pre-specified one-compartment population pharmacokinetic model. The key model parameters were the apparent total clearance (CL/F) of follitropin delta, the interindividual variability herein and the effects of baseline values of body weight, age, race, country/region, renal and hepatic function on CL/F. Renal function was assessed using the estimated glomerular filtration rate (eGFR) and hepatic function by alanine transaminase (ALT) and bilirubin levels. Main results and the role of chance The area under the FSH concentration-time curve during a dosing interval (AUC) was derived from dose and CL/F. Body weight was the covariate with the most pronounced effect on AUC, both in terms of the effect magnitude and statistical significance. AUC was 1.51-fold higher (90% confidence limits: 1.48; 1.54) in women with the lowest observed body weight of 40 kg compared to women with a typical body weight of 58 kg. The effect of renal function on AUC was small and in the same order of magnitude as the bioequivalence limits (0.8; 1.25). AUC was 1.28-fold higher (90% confidence limits: 1.23; 1.33) in women with the lowest observed eGFR value of 44 mL/min/1.73m2, compared to women with a typical eGFR value of 98 mL/min/1.73m2. The effects of Asian race and country/region (Japan, China, Other Asian) were confounded with each other and well within the bioequivalence limits when evaluated independently. The effects of age and the hepatic function markers ALT and bilirubin were well within the bioequivalence limits. Limitations, reasons for caution The women participating in the trials were generally healthy and the results cannot be transferred to women with renal or hepatic disease. A limited number of Black women contributed to the present analysis but the trend was similar. Data is forthcoming from ongoing trials including larger numbers of Black women. Wider implications of the findings: The findings support dosing follitropin delta by body weight and without adjustment for renal function, hepatic function, race, age or country/region. Trial registration number NCT01426386, NCT02309671, NCT01956110, NCT03228680 and NCT03296527

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