The protocol for patients undergoing kisspeptin triggering has been previously described.8 , 10 , 18 Patients triggered with hCG underwent either a GnRH agonist IVF protocol (long protocol), or a GnRH antagonist IVF protocol (short protocol), whereas all patients triggered with GnRHa or kisspeptin underwent the short protocol. Recombinant FSH (112.5‐250 IU Gonal F, Merck Serono, Geneva, Switzerland) was used to induce follicular growth in both long and short protocols. Premature ovulation was prevented by pretreatment with the GnRH agonist buserelin (0.2‐0.5 mg Suprefact, Sanofi‐Aventis, Gentily, France) in the long protocol, and with a GnRH antagonist—either cetrorelix (0.25 mg, Cetrotide, Merck Serono, Middlesex, UK) or ganirelix (0.25 mg Orgalutran, Merck Sharp & Dohme Ltd, Hertfordshire, UK) in the short protocol. The trigger was administered once 3 ovarian follicles were ≥18 mm in diameter and oocyte retrieval was conducted 36 hours thereafter. The trigger of oocyte maturation was either hCG—choriogonadotrophin alpha (0.25 mg, Ovitrelle; Merck Serono, Feltham, UK), GnRHa—buserelin acetate (2 mg, Suprecur, Sanofi‐Aventis, Guildford, UK), or kisspeptin‐54 (6.4‐12.8 nmol/kg as a single bolus, or 19.2 nmol/kg as a split dosing over 10 hours, Bachem Holding AG, Bubendorf, Switzerland) administered subcutaneously.8 , 10 , 18
Suprefact
Manufactured by Sanofi
Sourced in France, Germany, Italy
Suprefact is a laboratory reagent used in scientific research and experiments. It is a synthetic hormone that acts as a gonadotropin-releasing hormone agonist. The core function of Suprefact is to regulate and control the release of certain hormones in the body.
Automatically generated - may contain errors
Lab products found in correlation
Gonal f, by Merck Group (7 mentions)
Cetrotide, by Merck Group (4 mentions)
Ovitrelle, by Merck Group (4 mentions)
Pregnyl, by Merck Group (3 mentions)
Cetrorelix, by Merck Group (2 mentions)
Suprecur, by Sanofi (2 mentions)
Menopur, by Ferring (2 mentions)
Puregon, by Organon (2 mentions)
Ovidrel, by Merck Group (1 mentions)
Lucrin, by Abbott (1 mentions)
Pregnyl, by MSD (1 mentions)
Orgalutran, by MSD (1 mentions)
Synarela, by Pfizer (1 mentions)
Pregnyl, by Organon (1 mentions)
Ganirelix, by Organon (1 mentions)
Chloral hydrate, by Merck Group (1 mentions)
Leica dm irb, by Leica Microsystems (1 mentions)
Rfsh gonal f, by Merck Group (1 mentions)
Lutinus, by Ferring (1 mentions)
Progynova, by Bayer (1 mentions)
14 protocols using suprefact
1
Kisspeptin-Triggered Ovulation Induction Protocols
2
Ovarian Stimulation Protocol Comparison
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For the COH procedure, a combination of gonadotrophin was given with the long GnRH protocol using one of the following three regimens, that were (1) recombinant follicle stimulating hormone (rFSH) (Gonal F; Merck KGaA, Darmstadt, Germany), (2) GnRH agonist (Suprefact; Sanofi S.A., Paris, France), and (3) human chorionic gonadotropin (hCG) (Pregnyl; Merck KGaA) (Figure 1 ).
The GnRH agonist administered at a dose of 160 μg/day began in the middle of luteal phase in previous menstrual cycle and continues until the day before ovulation (about 14 days given). After E2 hormone levels are less than 70 pg/mL on the second day of menstruation, we combined the therapy with rFSH in each stimulated group. The first group received a dose of 30 IU, the second group received a dose of 50 IU, and the third group received a dose of 70 IU of rFSH. The rFSH was injected on the second day after menstruation at doses according to the treatment group for 10 days until the peak secretion of the E2 hormone occured. Furthermore, we administered 10000 IU of hCG, equivalent to 3200 IU. The luteal phase was determined by measuring serial P4 levels that begin on the postovulatory day.
The GnRH agonist administered at a dose of 160 μg/day began in the middle of luteal phase in previous menstrual cycle and continues until the day before ovulation (about 14 days given). After E2 hormone levels are less than 70 pg/mL on the second day of menstruation, we combined the therapy with rFSH in each stimulated group. The first group received a dose of 30 IU, the second group received a dose of 50 IU, and the third group received a dose of 70 IU of rFSH. The rFSH was injected on the second day after menstruation at doses according to the treatment group for 10 days until the peak secretion of the E2 hormone occured. Furthermore, we administered 10000 IU of hCG, equivalent to 3200 IU. The luteal phase was determined by measuring serial P4 levels that begin on the postovulatory day.
3
Ovarian Stimulation and Oocyte Retrieval Protocol
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Ovarian stimulation was achieved using a gonadotropin-releasing hormone (GnRH) agonist (Lucrin, Abbott Korea Ltd., Seoul, Korea; Suprefact, Sanofi-Aventis Deutschland GmbH, Frankfurt am Main, Germany) and GnRH antagonist (Cetrotide, Merck Serono, Geneva, Switzerland or Orgalutran, Schering-Plough Organon, Oss, the Netherlands). Recombinant human chorionic gonadotropin (hCG) (Ovidrel, Merck Serono) was administered subcutaneously in a single 225 IU dose when the dominant follicle reached a maximum diameter of 18 mm or greater. Vaginal ultrasound-guided follicle puncture was performed 34-36 hours after hCG injection. Retrieved oocytes were cultured for several hours in germinal vesicle (GV) series medium (Vitrolife, Kungsbacka, Sweden) at 37℃ in an atmosphere of 6% CO2 under humidified conditions. All oocyte handling procedures were conducted on warm stages using conventional methods.
4
Follicular Stimulation Protocol for Fertility Preservation
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Fertility preservation treatment with follicular stimulation using a GnRH-antagonist protocol was used in all patients (31, 32) . The stimulation, started within 2 to 4 days of the initial consultation, used recombinant follicle-stimulating hormone (FSH, Gonal-F; Merck-Serono) or urinary human menopausal gonadotropin (Repronex, Ferring Pharmaceuticals) (33) . An ultrasound examination was performed for follicular development monitoring.
Starting on day 6 of stimulation or when the leading follicle was >12 mm, a GnRH-antagonist in the form of 0.25 mg of ganirelix (Orgalutran; MSD Organon) or 0.25 mg of cetrorelix (Cetrotide; Merck-Serono) was added. Subcutaneous injection of 0.25 mg of recombinant human chorionic gonadotropin (Ovidrel, EMD Serono) or 1 mg of GnRHagonist buserelin (Suprefact; Sanofi-Aventis) as a trigger for final oocyte maturation was administered when two to three follicles reached 17 mm in diameter. Ultrasoundguided oocyte retrieval under conscious sedation was performed 36 hours later. Retrieved oocytes were either vitrified or fertilized (34, 35) .
Starting on day 6 of stimulation or when the leading follicle was >12 mm, a GnRH-antagonist in the form of 0.25 mg of ganirelix (Orgalutran; MSD Organon) or 0.25 mg of cetrorelix (Cetrotide; Merck-Serono) was added. Subcutaneous injection of 0.25 mg of recombinant human chorionic gonadotropin (Ovidrel, EMD Serono) or 1 mg of GnRHagonist buserelin (Suprefact; Sanofi-Aventis) as a trigger for final oocyte maturation was administered when two to three follicles reached 17 mm in diameter. Ultrasoundguided oocyte retrieval under conscious sedation was performed 36 hours later. Retrieved oocytes were either vitrified or fertilized (34, 35) .
5
Controlled Ovarian Stimulation Protocols
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Two types of protocol were used to achieve controlled ovarian stimulation; gonadotropin-releasing hormone (GnRH) antagonist short protocol or GnRH agonist long protocol. Orgalutran (MSD) or Cetrotide (Merck) was used in the antagonist protocol, and Synarela (Pfizer), Suprefact (Sanofi), or Suprecur (Sanofi) was used in the agonist protocol. Ovarian stimulation was performed with recombinant follicle-stimulating hormone (FSH) (Gonal-f; Merck), Puregon (MSD), Menopur (Ferring Pharmaceuticals), or Fostimon (NordicInfu Care), and the dosage was based on the woman's age, ovarian volume, baseline FSH level, and body mass index (BMI). Ovarian response was monitored by vaginal ultrasound to determine the count and size of the follicles. When two follicles had reached 17 mm an injection of human chorionic gonadotropin (hCG) (Ovitrelle, Merck; or Pregnyl, MSD) was given to induce final follicular maturation. Ovum pickup was conducted 35 hours after administration of hCG using a transvaginal ultrasound probe and needle (Cook Australia).
6
Controlled Ovarian Stimulation for IVF
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All patients were subjected to administration with the GnRH agonist Buserelin (Suprefact, Sanofi-Aventis, Italy, 0.2 ml/day) starting on day 21 of the previous cycle. Administration of 150 IU r-FSH/day (Gonal-f, Merck, Rome, Italy) was started at day 8 after Buserelin treatment and the follicular growth was monitored every two days using ultrasound and serum estradiol E2 levels, starting on day 6 of stimulation, modifying the dose of r-FSH as a consequence. The dose of 10,000 IU of hCG (Ovitrelle; Merck, Rome, Italy) was administered when at least 3 follicles showed a diameter ≥ 18 mm.
7
Controlled Ovarian Stimulation Protocol
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All women recruited were similarly treated with a GnRH agonist Buserelin (Suprefact, Sanofi-Aventis, Italy, 0.2 ml/day) administration, starting on day 21 of the previous cycle. Administration of 150-225 IU r-FSH/day (Gonal-f, Merck, Rome, Italy) was started at day 8 after GnRH agonist treatment and the follicular growth was monitored every two days using ultrasound and serum estradiol E2 levels, starting on day 6 of stimulation, modifying the dose of r-FSH as a consequence. The dose of 10, 000 IU of hCG (Ovitrelle; Merck, Rome, Italy) was administered when at least 3 follicles showed a diameter ≥ 18 mm.
8
GnRH Antagonist Ovarian Hyperstimulation Protocol
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Women underwent controlled ovarian hyperstimulation with a GnRH antagonist (cetrorelix; Merck Serono, Geneve, Switzerland; ganirelix; Organon, Oss, Netherlands) short protocol. For stimulation, recombinant FSH (rFSH) was used (Puregon; Organon; Gonal-F; Merck Serono). About 36 h before oocyte recovery HCG (5000-10,000 IU, im/sc; Pregnyl; Organon) or Buserelin (0.8 cc; Suprefact; Sanofi Aventis, Frankfurt, Germany) were administered. Estradiol serum levels were assayed at the day or one day before HCG or GnRH agonist administration [19 (link), 20 ].
9
Short GnRH-agonist Protocol for Controlled Ovarian Stimulation
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A short GnRH-agonist protocol was used: GnRH-agonist buserelin (Suprefact, Sanofi-Aventis) was started on cycle day 2 at a dose of 0.5 mg and was kept until triggering of final oocyte maturation with hCG. HMG (Menopur, Ferring) (21 women) or rFSH (Gonal F, Merck) (11 women) was administered on day 2 at a dose of 200 IU, and the dose was adjusted according to ovarian response on a daily basis. Serum E2 levels were measured daily starting on day 5 of ovarian stimulation with gonadotropins (day 7 of cycle) until the day of triggering final oocyte maturation with 10,000 IU of hCG (Pregnyl, Merck Sharp & Dohme) given intramuscularly. Follicular monitoring started on day 6 of stimulation (day 8 of cycle), and subsequent ultrasound scans were performed every day until oocyte retrieval. Follicular aspiration and oocyte retrieval took place 36 h after the administration of 10,000 IU hCG by transvaginal ultrasound-guided puncture. Luteal phase support was provided with 200 mg of micronized progesterone administered intravaginally three times daily from the day after egg collection onwards, and serum hCG was measured 14 days later. Ultrasound scans, oocyte retrievals, and embryo-transfers were conducted by two fertility specialists of the centre. Similarly, oocyte grading, fertilization, early embryo development, and embryo grading were conducted by two senior embryologists of the centre.
10
Buserelin Administration in Rats
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Rats (n=12) were administered 20 μg of the GnRH analog buserelin (1 mg/ml) (Suprefact, Sanofi-Aventis, Bromma, Sweden) (dissolved in 0.2 ml saline) subcutaneously, once daily for 5 days, followed by 3 weeks of recovery, representing one session of treatment (4 (link)). The dosage and administration of buserelin are based on previous studies which have shown reliable physiological effects in terms of uterine hypertrophy, without any adverse effects (4 (link),10 (link),13 (link)). Control animals (n=8) received 0.2 ml saline injections. The animals were weighed prior to inclusion in the study, and weekly in the morning during the study. Thirty-two weeks after the start of the study, and 4 months after the last treatment session, rats were anesthetized using chloral hydrate (300 mg/kg body weight; C8383; Sigma-Aldrich, St. Louis, MO, USA) and killed by aorta puncture. Tissue samples from the fundus, distal ileum, proximal colon, and distal part of the uterine horn were collected and processed for histological evaluation.
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