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Patients will be divided into two groups Group A; patients using long protocol and freeze all embryos Group B; patients using antagonist protocol with fresh embryo transfer Patients will be carefully chosen according to a strict inclusion and exclusion criteria after meticulous revision of patient files.
In the long protocol, daily SC injection of Triptorelin :Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG triggering. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a starting dose of 150-300 IU/day according to women age, day 3 FSH,AMH and previous gonadotropin response then adjustment of the dose according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days according to the ovarian response to treatment starting on treatment cycle day (6) for folliculometry and endometrial thickness and pattern.
Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when 2 or more follicles have 18 mm as a mean diameter .
Flexible GnRH antagonist protocol was done with daily s.c administration of cetrorelix 0.25 mg (Cetrotide, Merck Serono, Darmstadt, Germany) started when one or more of the following criteria were achieved: (i) one or more follicle reached 14 mm diameter; (ii) The level of serum E2 reached 600 pg/ml; and (iii) The level of serum LH levels reached 10 IU/l . Daily sc rFSH (Gonal-f; Merck Serono , Darmstadt, Germany) injections was started on 2nd day of the cycle in the antagonist protocol. Continuation of rFSH and GnRH antagonist daily until triggering day was done.
Patients will be divided into two groups Group A; patients using long protocol and freeze all embryos Group B; patients using antagonist protocol with fresh embryo transfer Patients will be carefully chosen according to a strict inclusion and exclusion criteria after meticulous revision of patient files.
In the long protocol, daily SC injection of Triptorelin :Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG triggering. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l with either HMG(Menogon; Ferring, Switzerland) or rFSH (Gonal-f; Merck Serono, Germany) in a starting dose of 150-300 IU/day according to women age, day 3 FSH,AMH and previous gonadotropin response then adjustment of the dose according to ovarian response monitored by serum E2 and ultrasound evaluation. All patients were followed up by Transvaginal ultrasound scan daily or on alternate days according to the ovarian response to treatment starting on treatment cycle day (6) for folliculometry and endometrial thickness and pattern.
Triggering by HCG 10000 IU IM (Pregnyl, Organon, the Netherlands) when 2 or more follicles have 18 mm as a mean diameter .
Flexible GnRH antagonist protocol was done with daily s.c administration of cetrorelix 0.25 mg (Cetrotide, Merck Serono, Darmstadt, Germany) started when one or more of the following criteria were achieved: (i) one or more follicle reached 14 mm diameter; (ii) The level of serum E2 reached 600 pg/ml; and (iii) The level of serum LH levels reached 10 IU/l . Daily sc rFSH (Gonal-f; Merck Serono , Darmstadt, Germany) injections was started on 2nd day of the cycle in the antagonist protocol. Continuation of rFSH and GnRH antagonist daily until triggering day was done.
Cycle cancellation was decided when transvaginal ultrasound scan on cycle day (9) revealed no adequate follicular growth (<3 mature follicles),if no oocytes were retrieved on ovum pick up,or if failure of fertilization occurred. If signs of early OHSS were observed at 3rd day of ovum pickup ,cancellation of ET was done with elective embryo cryopreservation as it may end with life-threatening OHSS . ET was cancelled also if any criteria of hospital admission was found
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Long GnRH agonist | Active Comparator | daily SC injection of Triptorelin :Decapeptyl 0.1 mg (Ferring, Switzerland) 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG triggering. Gn stimulation started after fulfilling stimulation start criteria of thin endometrium < 5 mm and low E2 < 50 and LH < 5IU/l with either HMG or rFSH in a starting dose of 150-300 IU/day |
|
| GnRH antagonist | Active Comparator | Flexible GnRH antagonist protocol was done with daily s.c administration of cetrorelix 0.25 mg started when one or more of the following criteria were achieved: (i) one or more follicle reached 14 mm diameter; (ii) The level of serum E2 reached 600 pg/ml; and (iii) The level of serum LH levels reached 10 IU/l. Daily sc rFSH injections was started on 2nd day of the cycle in the antagonist protocol. Continuation of rFSH and GnRH antagonist daily until triggering day was done |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Triptorelin | Drug | daily SC injection of Triptorelin 0.1 mg started at day 21 of the cycle prior to stimulation cycle and continued till the day of hCG triggering. |
|
| Measure | Description | Time Frame |
|---|---|---|
| clinical pregnancy rate | The detection of fetal cardiac activity within a gestational sac on ultrasonography examinationenlargement (<12 cm in average diameter), ascitis in moderate form and clinical evidence of ascites and/or hydrothorax, haemoconcentration and significant ovarian enlargement (>12 cm in average diameter) | 4 weeks after embryo transfer |
| Measure | Description | Time Frame |
|---|---|---|
| chemical pregnancy rate | POSITIVE pregnancy testing of HCG exceeding 50 mIU | 14 days after embryo transfer |
| abortion rate | termination of pregnancy before 12 weeks of gestational age |
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Inclusion Criteria:
Exclusion criteria;
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| Name | Affiliation | Role |
|---|---|---|
| Ahmed Maged, MD | Kasr Alainy medical school | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Ahmed Maged | Cairo | 12151 | Egypt |
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| ID | Term |
|---|---|
| D017329 | Triptorelin Pamoate |
| C062876 | cetrorelix |
| D015292 | Glycoprotein Hormones, alpha Subunit |
| C571801 | follitropin alfa |
| ID | Term |
|---|---|
| D007987 | Gonadotropin-Releasing Hormone |
| D010906 | Pituitary Hormone-Releasing Hormones |
| D007028 | Hypothalamic Hormones |
| D036361 | Peptide Hormones |
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|
| cetrorelix | Drug | Flexible GnRH antagonist protocol was done with daily s.c administration of cetrorelix 0.25 mg started when one or more of the following criteria were achieved: (i) one or more follicle reached 14 mm diameter; (ii) The level of serum E2 reached 600 pg/ml; and (iii) The level of serum LH levels reached 10 IU/l . |
|
|
| Recombinant Follicle Stimulating Hormone | Drug | Daily sc rFSH (Gonal-f; Merck Serono , Darmstadt, Germany) injections was started on 2nd day of the cycle in the antagonist protocol. Continuation of rFSH and GnRH antagonist daily until triggering day was done. |
|
|
| 12 weeks of gestational age |
| Ovarian hyperstimulation syndrome | evaluated by the British fertility society criteria, the Canadian Fertility and Andrology Society ( CFAS) and the Society of obstetrics and Gynecology of Canada (SOGC); [Mild OHSS; Abdominal bloating, Mild abdominal pain, Ovarian size usually < 8 cm. Moderate OHSS; Moderate abdominal pain, Nausea with/without vomiting, Ultrasound evidence of ascites and Ovarian size usually 8-12 cm. Severe OHSS; Clinical ascites (occasionally pleural effusion), Oliguria, Hemoconcentration with hematocrit (> 45%), Hypoproteinemia and Ovarian size usually > 12 cm. Critical OHSS; Tense ascites or large pleural effusion, Hematocrit (> 55%) White cell count > 25 000/L, anuria, Thromboembolism or Acute respiratory distress syndrome](streamdown:incomplete-link) | 7 days after HCG administration |
| Late Ovarian hyperstimulation syndrome | OHSS manifestation 12 to 17 days following HCG administration | 12 to 17 days following HCG administration |
| D006728 | Hormones |
| D006730 | Hormones, Hormone Substitutes, and Hormone Antagonists |
| D009479 | Neuropeptides |
| D010455 | Peptides |
| D000602 | Amino Acids, Peptides, and Proteins |
| D009842 | Oligopeptides |
| D009419 | Nerve Tissue Proteins |
| D011506 | Proteins |
| D006063 | Chorionic Gonadotropin |
| D006062 | Gonadotropins |
| D005640 | Follicle Stimulating Hormone |
| D006065 | Gonadotropins, Pituitary |
| D007986 | Luteinizing Hormone |
| D010908 | Pituitary Hormones, Anterior |
| D010907 | Pituitary Hormones |
| D013972 | Thyrotropin |
| D010926 | Placental Hormones |