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11 protocols using orgalutran

1

GnRH Antagonist Stimulation Protocol

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Hormonal stimulation was performed in GnRH antagonist protocols with recombinant FSH (Puregon®, MSD; Gonal F®, MerckSerono) or human menopausal gonadotropin (Menogon® or Menopur®, Ferring). The starting dosage was chosen according to the results of the anti-Müllerian hormone and antral follicle count (14 (link)). Starting on day 5, patients received a daily dosage of 0.25 mg GnRH antagonist (Orgalutran®, MSD or Cetrotide®, MERCK) to prevent premature ovulation.
During the stimulation course, stimulation dosage was adapted to the individual patient’s response. GnRH agonist trigger for final oocyte maturation was used to avoid OHSS as the ultrasound showed >13 follicles with a size of ≥11 mm (13 (link)). Patients received 0.3 mg of Triptorelin (Decapeptyl®, Ferring) for final oocyte maturation, as soon as ≥3 follicles were ≥17 mm in diameter. OPU was performed 36 h later under mild sedation, aspirating all follicles of a size of ≥11 mm.
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2

Ovarian Stimulation and Oocyte Retrieval

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The ovarian stimulation was initiated from day 3 of the menstrual cycle and continued until the day that ovulation was induced. The standard daily starting dose of recombinant human FSH (Gonal-F®; Merck Serono) or (Puregon®; MSD) was 150–225 IU, depending on patient age, BMI, antral follicle count, and basal serum FSH levels. After 5 days, doses were adjusted according to ovarian response. Once the leading follicle had reached a size of 13 mm, co-treatment with a GnRH antagonist (Cetrotide® 0.25 mg; Merck Serono) or (Orgalutran® 0.25 mg; MSD) was initiated and continued up until and including the day of induction of ovulation. When at least three follicles had reached a size of 17 mm, ovulation induction was performed with a single bolus of 0.2 mg triptorelin, s.c. (Decapeptyl® 0.1 mg, Ipsen, France), followed by OPU 36 h later. Retrieved oocytes were fertilized by either IVF or ICSI, depending on sperm quality.
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3

GnRH-antagonist Protocol for Ovulation Trigger

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A daily dose (0.25mg) of GnRH-ant (Orgalutran®, MSD, Netherlands) was used on the fifth or sixth day of gonadotropin until the trigger day.
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4

Controlled Ovarian Stimulation Protocols

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On Day 2 of the menstrual cycle patients were administered either a single subcutaneous dose of 150 μg CFA (Elonva®; MSD, Oss, The Netherlands) or started a course of seven fixed daily doses of 300 IU up to 450 IU of hp-hMG (Menopur®; Ferring, Saint-Prex, Switzerland). In the CFA/hp-hMG group, daily doses of ≥300 IU of hp-hMG were administered from Day 8 of stimulation until the day of ovulation triggering, when required. Hp-hMG dose was adjusted according to the stimulation response that was monitored with serial measurements of serum estradiol and transvaginal ultrasonic evaluation of follicle number and size.
Pituitary down-regulation was performed with daily administration of GnRH-antagonist (ganirelix; Orgalutran®; MSD, Oss, The Netherlands) starting on Day 6 of stimulation.
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5

Ovarian Stimulation and Insemination Protocol

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Ovarian stimulation used a combination of recombinant FSH (Gonal F, Merck, Lyon, France or Puregon, MSD, Paris, France) and GnRH antagonist (Cetrotide 0.25 mg, Merck, Lyon, France or Orgalutran, MSD, Paris, France). The initial dose of FSH was chosen according the female age and the score described by Chalumeau et al. [26 (link)]. Ovulation was triggered with recombinant hCG (Ovitrelle, Merck, Lyon, France) when at least one follicle ≥ 18 mm was obtained. Insemination was performed 36 h after hCG injection. A luteal support of 400 mg per day of intra-vaginal progesterone was administrated during 15 days, starting on the day of insemination.
Clinical pregnancy was defined as the presence of a fetal heartbeat evaluated during the transvaginal ultrasonographic examination seven weeks after insemination. Live birth was defined as the delivery of at least one live born infant after a 22 weeks or more pregnancy [27 (link)].
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6

GnRH Antagonist Protocol for Ovarian Stimulation

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All patients followed a GnRH antagonist protocol. Ovarian stimulation was initiated with recombinant FSH (Puregon; MSD, Turkey or Gonal-F; Merck Serono, Turkey) on day 2 or 3 of the cycle and continued until the day of ovulation trigger. Cycles were monitored using ultrasound scanning. A GnRH antagonist, either ganirelix (Orgalutran; MSD, Turkey) or cetrorelix (Cetrotide; Merck Serono, Turkey), was administered when the leading follicle attained a maximum diameter of 14 mm. When at least two follicles had reached diameters of 17 mm, final oocyte maturation was triggered by administering 0.2 mg of the GnRHa triptorelin (Gonapeptyl; Ferring, Turkey) in Group 1 or recombinant hCG (Ovitrelle; Merck Serono, Turkey) in Group 2.
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7

Ovarian Stimulation and Assisted Reproduction

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Ovarian stimulation used a combination of recombinant FSH (Gonal F, Merck, Lyon, France or Puregon, MSD, Paris, France) and GnRH antagonist (Cetrotide 0.25 mg, Merck, Lyon, France or Orgalutran, MSD, Paris, France). Ovulation was triggered with recombinant hCG (Ovitrelle, Merck, Lyon, France) when at least one follicle ≥ 18 mm was obtained. Insemination was performed 36 h after hCG injection. A luteal support of 400 mg per day of intra-vaginal progesterone.
Clinical pregnancy was defined as the presence of a fetal heartbeat seven weeks after insemination. Live birth was defined as the delivery of at least one live born infant after a 22 weeks or more pregnancy [16 (link)].
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8

Antagonist Protocol for Controlled Ovarian Stimulation

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The antagonist protocol was started from day 2 of menstruation using 225 units of human menopausal gonadotrophins (hMG) per day (IVF-M, LG Life Sciences, Iksan-si, Korea). The gonadotropin-releasing hormone (GnRH) antagonist (Orgalutran, MSD, Ravensburg, Germany) was injected between stimulation days 7–9. Oocyte maturation was induced with human chorionic gonadotropin (hCG) treatment (IVF-C, LG Life Sciences, Iksan-si, Korea). Oocytes were picked up 36–37 hours later and intra-cytoplasmic sperm injection (ICSI) was performed within 6 hours. All embryos were doubly biopsied in trophectoderm at blastocyst stages. All embryos were cryopreserved with the vitrified method.
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9

Controlled Ovarian Stimulation Protocols

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Both the standard GnRH agonist and antagonist protocol were used for controlled ovarian stimulation. Briefly, the long GnRH agonist protocol was based on the administration of daily leuprorelin (Enantone die; Takeda) or triptorelin (Fertipeptil; Ferring) in the mid-luteal phase before the stimulation cycle. The administration of recombinant FSH (rFSH; GonalF [Merck Serono] or Puregon [MSD]), hMG (Meropur, Ferring), or urinary FSH (Fostimon; IBSA) was started when pituitary desensitization was achieved ($14 days after the initiation of GnRH agonists), as evidenced by the absence of ovarian follicles >10 mm and endometrial thickness <4 mm on transvaginal ultrasound examination. In the GnRH antagonist protocol (Cetrotide [Merck Serono] or Orgalutran [MSD]) treatment with FSH or hMG was started on day 2-3 of the stimulation cycle, and the GnRH antagonist was added when one or more follicles had reached a diameter R14 mm. The starting dose of FSH/hMG was based on age, body weight, and ovarian reserve, ranging from 100 to 225 IU/d, per the internal protocol of the clinic. An ovarian ultrasound was performed on stimulation day 5-6, and gonadotropin doses were adjusted according to the ovarian response. When at least one follicle reached R18 mm, 10,000 IU hCG or 250 mg recombinant hCG was administrated; 34-36 hours later, follicles were aspirated under patient sedation.
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10

Growth Hormone Addition in Older IVF Patients

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Patient treatment consisted of two types of GnRH-LH suppression (Orgalutran [MSD] and Cetrotide [Merck Serono]) in conjunction with commercially prepared rFSH (Puregon [MSD] and Gonal-f [Merck Serono]), from cycle day 2 for approximately 10 days, as described by Regan et al. (34) . The dosages of rFSH were administered according to a well-described and validated algorithm designed to collect 10 AE 2 oocytes and avoid ovarian hyperstimulation syndrome (36) . Ovulation was triggered with 10,000 IU hCG (Pregnyl, MSD), and oocyte retrieval was 36 hours later by transvaginal oocyte aspiration (33) . Patients classified as poor prognosis due to poor ovarian response or with three or more failed attempts to conceive through IVF treatment with gonadotrophin alone were co-treated with a total of 60 IU GH (Saizen, Serono) over a period of 20-24 days in the lead-up to IVF. Specifically, a total of six injections of GH was administered to 10 patients on day 21 of the preceding cycle, and on days 2, 6, 8, 10, and 12 of the ensuing IVF cycle (10 IU per injection, a total of 60 IU). The women were aged R39 years and had at least one failed IVF cycle (18) .
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