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| ID | Type | Description | Link |
|---|---|---|---|
| 2013-001669-17 | EudraCT Number | ||
| U1111-1147-6826 | Other Identifier | WHO |
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This trial investigates the effects of FE 999049 compared to GONAL-F.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| A | Experimental | Follitropin Delta (FE 999049) |
|
| B | Active Comparator | Follitropin Alfa (GONAL-F) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Follitropin Delta (FE 999049) | Drug |
| ||
| Follitropin Alfa (GONAL-F) |
| Measure | Description | Time Frame |
|---|---|---|
| Ongoing Pregnancy Rate | Ongoing pregnancy was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer. | 10-11 weeks after blastocyst transfer |
| Ongoing Implantation Rate | Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred. | 10-11 weeks after blastocyst transfer |
| Measure | Description | Time Frame |
|---|---|---|
| Vital Pregnancy Rate | Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer. | 5-6 weeks after blastocyst transfer |
| Implantation Rate |
Not provided
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Clinical Development Support | Ferring Pharmaceuticals | Study Director |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| UZ Brussel (there may be other sites in this country) | Brussels | Belgium | ||||
| Fertilitat and PUC-RS (there may be other sites in this country) |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 32819842 | Result | Arce JC, Larsson P, Garcia-Velasco JA. Establishing the follitropin delta dose that provides a comparable ovarian response to 150 IU/day follitropin alfa. Reprod Biomed Online. 2020 Oct;41(4):616-622. doi: 10.1016/j.rbmo.2020.07.006. Epub 2020 Jul 15. | |
| 34254211 | Result | Havelock J, Aaris Henningsen AK, Mannaerts B, Arce JC; ESTHER-1 and ESTHER-2 Trial Groups. Pregnancy and neonatal outcomes in fresh and frozen cycles using blastocysts derived from ovarian stimulation with follitropin delta. J Assist Reprod Genet. 2021 Oct;38(10):2651-2661. doi: 10.1007/s10815-021-02271-5. Epub 2021 Jul 13. |
Not provided
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A total of 1501 subjects were screened in the trial, of whom 1329 subjects were randomised: 666 subjects to FE 999049 and 663 subjects to GONAL-F. Three subjects were randomisation failures and did not receive investigational medicinal product (IMP); 1 in the FE 999049 group and 2 in the GONAL-F group.
A total of 37 sites randomised subjects into the trial : 3 in Belgium, 3 in Brazil, 3 in Canada, 4 in the Czech Republic, 2 in Denmark, 2 in France, 2 in Italy, 2 in Poland, 4 in Russia, 10 in Spain and 2 in United Kingdom.
Not provided
| ID | Title | Description |
|---|---|---|
| FG000 | FE 999049 | FE 999049 was administered as single daily subcutaneous injections in the abdomen. Subjects randomised to FE 999049 had their individual dose determined on the basis of their anti-Müllerian hormone (AMH) level at screening and their body weight at randomisation. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days. |
| FG001 | GONAL-F | Follitropin Alfa (GONAL-F) was administered as single daily subcutaneous injections in the abdomen. The starting dose of GONAL-F was 150 international units (IU) and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 450 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days. |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
Of the 1,329 randomised subjects, 1,326 were exposed to IMP: FE 999049 (665 subjects) and GONAL-F (661 subjects). The 3 subjects who were not exposed to IMP were randomisation failures; 2 subjects (1 in each treatment group) did not fulfil an inclusion criterion, and 1 subject (in the GONAL-F group) withdrew due to personal reasons.
Not provided
| ID | Title | Description |
|---|---|---|
| BG000 | FE 999049 | FE 999049 was administered as single daily subcutaneous injections in the abdomen. Subjects randomised to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomisation. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days. |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Categorical | Count of Participants |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | Ongoing Pregnancy Rate | Ongoing pregnancy was defined as at least one intrauterine viable fetus 10-11 weeks after blastocyst transfer. | Modified intention-to-treat (mITT) analysis set (all randomised and exposed subjects). This is equivalent to full analysis set (FAS). | Posted | Number | Percentage of subjects | 10-11 weeks after blastocyst transfer |
|
Adverse events (AEs) were recorded from signed informed consent to the end-of-trial (up to approximately 5.5 months).
AEs with onset after start of first administration of IMP were considered treatment-emergent and are presented for the safety analysis set.
Not provided
| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | FE 999049 | FE 999049 was administered as single daily subcutaneous injections in the abdomen. Subjects randomised to FE 999049 had their individual dose determined on the basis of their AMH level at screening and their body weight at randomisation. The daily FE 999049 dose was fixed throughout the stimulation period and maximum allowed daily dose was 12 μg. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Post procedural haemorrhage | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Procedural pain | Injury, poisoning and procedural complications | MedDRA 17.1 | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Global Clinical Compliance | Ferring Pharmaceuticals | DK0-Disclosure@ferring.com |
Not provided
| ID | Term |
|---|---|
| D007246 | Infertility |
| ID | Term |
|---|---|
| D000091662 | Genital Diseases |
| D000091642 | Urogenital Diseases |
Not provided
Not provided
| ID | Term |
|---|---|
| C000620228 | follitropin delta |
| C000608977 | FE 999049 |
| C571801 | follitropin alfa |
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
|
Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred.
| 5-6 weeks after blastocyst transfer |
| Proportion of Subjects With Extreme Ovarian Responses, Defined as <4, ≥15 or ≥20 Oocytes Retrieved | Day of oocyte retrieval |
| Proportion of Subjects With Early OHSS (Ovarian Hyperstimulation Syndrome) and/or Preventive Interventions for Early OHSS | The proportion of subjects with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented. | ≤9 days after triggering of final follicular maturation |
| Proportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response | Proportion of subjects with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with gonadotropin-releasing hormone (GnRH) agonist are presented. | End-of-stimulation (up to 20 stimulation days) |
| Number of Oocytes Retrieved | Day of oocyte retrieval |
| Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | Day of oocyte retrieval |
| Percentage of Metaphase II Oocytes (Oocytes Inseminated Using ICSI [Intracytoplasmic Sperm Injection]) | Number of oocytes in metaphase II prior to ICSI insemination is presented. | Prior to insemination |
| Fertilisation Rate | Fertilisation rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved. | Day 1 after insemination |
| Number and Quality of Embryos on Day 3 | Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and fragmentation ≤20% on Day 3. | On day 3 after oocyte retrieval |
| Number and Quality of Blastocysts on Day 5 | Number of blastocysts (total and good-quality) on Day 5 are presented. A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher. | On day 5 after oocyte retrieval |
| Total Gonadotropin Dose | The total gonadotropin dose was recorded. | End-of-stimulation (up to 20 stimulation days) |
| Number of Stimulation Days | End-of-stimulation (up to 20 stimulation days) |
| Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments | End-of-stimulation (up to 20 stimulation days) |
| Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | Subjects self-assessed injection site reactions (redness, itching, pain, swelling and bruising) immediately, 30 minutes and 24 hours after each injection. The injection site reactions were assessed as none, mild, moderate and severe. The frequency of injection site reactions (mild, moderate or severe) based on all assessments performed is presented. | End-of-stimulation (up to 20 stimulation days) |
| Abdominal Discomfort Related to Controlled Ovarian Stimulation as Assessed by a Visual Analogue Scale (VAS) | The subject self-assessed abdominal discomfort related to controlled ovarian stimulation using a VAS going from 0 mm (no abdominal discomfort) to 100 mm (worst imaginable abdominal discomfort). | End-of-stimulation and day of blastocyst transfer |
| Changes in Body Weight | Change in body weight from baseline to end-of-stimulation and from baseline to day of blastocyst transfer. | End-of-stimulation and day of blastocyst transfer |
| Changes in Maximum Abdominal Circumference | Change in maximum abdominal circumference from baseline to end-of-stimulation and from baseline to day of blastocyst transfer. | End-of-stimulation and day of blastocyst transfer |
| Proportion of Subjects With Treatment-induced Anti-follicle-stimulating Hormone (FSH) Antibodies | The proportion of subjects with at least one treatment-induced anti-FSH antibody response at any time point. | Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose |
| Proportion of Subjects With Late OHSS | Late OHSS was defined as OHSS with onset >9 days after triggering of final follicular maturation.The proportion of subjects with late OHSS, and late OHSS of moderate or severe grade are presented. | >9 days after triggering of final follicular maturation |
| Technical Malfunctions of the Administration Pen | Confirmed technical malfunction of administration pen. | End-of-stimulation (up to 20 stimulation days) |
| Porto Alegre |
| Brazil |
| Pacific Centre for Reproductive Medicine | Burnaby | British Columbia | Canada |
| Olive Fertility Centre | Vancouver | British Columbia | Canada |
| Ottawa Fertility Centre | Ottawa | Ontario | Canada |
| IVF CUBE SE (there may be other sites in this country) | Prague | Czechia |
| Rigshospitalet Fertilitetsklinikken (there may be other sites in this country) | Copenhagen | Denmark |
| Department of Endocrine Gynaecology and Reproductive Medicine, Hôpital Jeanne de Flandre (there may be other sites in this country) | Lille | France |
| Centro Natalità San Raffaele (there may be other sites in this country) | Milan | Italy |
| The nOvum Clinic (there may be other sites in this country) | Warsaw | Poland |
| IVF & Reproductive Genetics Center (there may be other sites in this country) | Moscow | Russia |
| IVI Sevilla (there may be other sites in this country) | Seville | Spain |
| Glasgow Centre for Reproductive Medicine Ltd. (there may be other sites in this country) | Glasgow | United Kingdom |
| 34799275 | Result | Ishihara O, Nelson SM, Arce JC. Comparison of ovarian response to follitropin delta in Japanese and White IVF/ICSI patients. Reprod Biomed Online. 2022 Jan;44(1):177-184. doi: 10.1016/j.rbmo.2021.09.014. Epub 2021 Sep 23. |
| 30801744 | Derived | Nelson SM, Larsson P, Mannaerts BMJL, Nyboe Andersen A, Fauser BCJM. Anti-Mullerian hormone variability and its implications for the number of oocytes retrieved following individualized dosing with follitropin delta. Clin Endocrinol (Oxf). 2019 May;90(5):719-726. doi: 10.1111/cen.13956. Epub 2019 Mar 18. |
| 27912901 | Derived | Nyboe Andersen A, Nelson SM, Fauser BC, Garcia-Velasco JA, Klein BM, Arce JC; ESTHER-1 study group. Individualized versus conventional ovarian stimulation for in vitro fertilization: a multicenter, randomized, controlled, assessor-blinded, phase 3 noninferiority trial. Fertil Steril. 2017 Feb;107(2):387-396.e4. doi: 10.1016/j.fertnstert.2016.10.033. Epub 2016 Nov 29. |
| Personal reasons |
|
| BG001 | GONAL-F | GONAL-F was administered as single daily subcutaneous injections in the abdomen. The starting dose of GONAL-F was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 450 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days. |
| BG002 | Total | Total of all reporting groups |
| Participants |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| OG001 | GONAL-F | GONAL-F was administered as single daily subcutaneous injections in the abdomen. The starting dose of GONAL-F was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 450 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days. |
|
|
|
| Primary | Ongoing Implantation Rate | Ongoing implantation rate was defined as the number of intrauterine viable fetuses 10-11 weeks after transfer divided by number of blastocysts transferred. | Subjects with blastocyst transfer (a total of 585 and 584 blastocysts were transferred in the FE999049 and GONAL-F groups, respectively). | Posted | Number | Percentage | 10-11 weeks after blastocyst transfer |
|
|
|
|
| Secondary | Vital Pregnancy Rate | Vital pregnancy was defined as at least one intrauterine gestational sac with fetal heart beat 5-6 weeks after blastocyst transfer. | mITT analysis set (all randomised and exposed subjects). This is equivalent to the FAS. | Posted | Number | Percentage of subjects | 5-6 weeks after blastocyst transfer |
|
|
|
|
| Secondary | Implantation Rate | Implantation rate was defined as the number of gestational sacs 5-6 weeks after transfer divided by number of blastocysts transferred. | Subjects with blastocyst transfer (a total of 585 and 584 blastocysts were transferred in the FE999049 and GONAL-F groups, respectively). | Posted | Number | Percentage | 5-6 weeks after blastocyst transfer |
|
|
|
|
| Secondary | Proportion of Subjects With Extreme Ovarian Responses, Defined as <4, ≥15 or ≥20 Oocytes Retrieved | Subjects who underwent triggering of final follicular maturation. | Posted | Number | Percentage of subjects | Day of oocyte retrieval |
|
|
|
|
| Secondary | Proportion of Subjects With Early OHSS (Ovarian Hyperstimulation Syndrome) and/or Preventive Interventions for Early OHSS | The proportion of subjects with early OHSS, early OHSS of moderate or severe grade, preventive interventions for early OHSS, early OHSS and/or preventive interventions for early OHSS, and early OHSS of moderate or severe grade and/or preventive interventions for early OHSS are presented. | mITT analysis set (all randomised and exposed subjects). This is equivalent to the FAS. | Posted | Number | Percentage of subjects | ≤9 days after triggering of final follicular maturation |
|
|
|
|
| Secondary | Proportion of Subjects With Cycle Cancellation Due to Poor Ovarian Response or Excessive Ovarian Response | Proportion of subjects with cycle cancellation due to poor ovarian response, excessive ovarian response, and triggering with gonadotropin-releasing hormone (GnRH) agonist are presented. | mITT analysis set (all randomised and exposed subjects). This is equivalent to the FAS. | Posted | Number | Percentage of subjects | End-of-stimulation (up to 20 stimulation days) |
|
|
|
|
| Secondary | Number of Oocytes Retrieved | Subjects who underwent triggering of final follicular maturation. | Posted | Mean | Standard Deviation | Oocytes retrieved | Day of oocyte retrieval |
|
|
|
|
| Secondary | Proportion of Subjects With <4, 4-7, 8-14, 15-19 and ≥20 Oocytes Retrieved | Subjects who underwent triggering of final follicular maturation. | Posted | Number | Percentage of subjects | Day of oocyte retrieval |
|
|
|
|
| Secondary | Percentage of Metaphase II Oocytes (Oocytes Inseminated Using ICSI [Intracytoplasmic Sperm Injection]) | Number of oocytes in metaphase II prior to ICSI insemination is presented. | Subjects with all oocytes inseminated using ICSI. | Posted | Mean | Standard Deviation | Number of oocytes | Prior to insemination |
|
|
|
|
| Secondary | Fertilisation Rate | Fertilisation rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved. | Subjects with oocytes retrieved. | Posted | Mean | Standard Deviation | Percentage of oocytes | Day 1 after insemination |
|
|
|
|
| Secondary | Number and Quality of Embryos on Day 3 | Number of embryos (total and good-quality) on Day 3 are presented. A good-quality embryo was defined as an embryo with ≥6 blastomeres and fragmentation ≤20% on Day 3. | Subjects with oocytes retrieved. | Posted | Mean | Standard Deviation | Number of embryos | On day 3 after oocyte retrieval |
|
|
|
|
| Secondary | Number and Quality of Blastocysts on Day 5 | Number of blastocysts (total and good-quality) on Day 5 are presented. A good-quality blastocyst was defined as a blastocyst of grade 3BB or higher. | Subjects with oocytes retrieved. | Posted | Mean | Standard Deviation | Number of blastocytss | On day 5 after oocyte retrieval |
|
|
|
|
| Secondary | Total Gonadotropin Dose | The total gonadotropin dose was recorded. | mITT analysis set (all randomised and exposed subjects). This is equivalent to the FAS. | Posted | Mean | Standard Deviation | µg of dose | End-of-stimulation (up to 20 stimulation days) |
|
|
|
|
| Secondary | Number of Stimulation Days | mITT analysis set (all randomised and exposed subjects). This is equivalent to the FAS. | Posted | Mean | Standard Deviation | Days | End-of-stimulation (up to 20 stimulation days) |
|
|
|
|
| Secondary | Proportion of Subjects With Investigator-requested Gonadotropin Dose Adjustments | mITT analysis set (all randomised and exposed subjects). This is equivalent to the FAS. | Posted | Number | Percentage of subjects | End-of-stimulation (up to 20 stimulation days) |
|
|
|
|
| Secondary | Frequency of Injection Site Reactions (Redness, Pain, Itching, Swelling and Bruising) Assessed by the Subject During the Stimulation Period | Subjects self-assessed injection site reactions (redness, itching, pain, swelling and bruising) immediately, 30 minutes and 24 hours after each injection. The injection site reactions were assessed as none, mild, moderate and severe. The frequency of injection site reactions (mild, moderate or severe) based on all assessments performed is presented. | Safety analysis set (all randomised and exposed subjects). This is equivalent to the mITT (FAS). | Posted | Number | Percentage of events | End-of-stimulation (up to 20 stimulation days) |
|
|
|
| Secondary | Abdominal Discomfort Related to Controlled Ovarian Stimulation as Assessed by a Visual Analogue Scale (VAS) | The subject self-assessed abdominal discomfort related to controlled ovarian stimulation using a VAS going from 0 mm (no abdominal discomfort) to 100 mm (worst imaginable abdominal discomfort). | Safety analysis set (all randomised and exposed subjects). This is equivalent to the mITT (FAS). | Posted | Mean | Standard Deviation | Millimeter | End-of-stimulation and day of blastocyst transfer |
|
|
|
| Secondary | Changes in Body Weight | Change in body weight from baseline to end-of-stimulation and from baseline to day of blastocyst transfer. | Safety analysis set (all randomised and exposed subjects). This is equivalent to the mITT (FAS). | Posted | Mean | Standard Deviation | Kg | End-of-stimulation and day of blastocyst transfer |
|
|
|
| Secondary | Changes in Maximum Abdominal Circumference | Change in maximum abdominal circumference from baseline to end-of-stimulation and from baseline to day of blastocyst transfer. | Safety analysis set (all randomised and exposed subjects). This is equivalent to the mITT (FAS). | Posted | Mean | Standard Deviation | Centimeter | End-of-stimulation and day of blastocyst transfer |
|
|
|
| Secondary | Proportion of Subjects With Treatment-induced Anti-follicle-stimulating Hormone (FSH) Antibodies | The proportion of subjects with at least one treatment-induced anti-FSH antibody response at any time point. | Safety analysis set (all randomised and exposed subjects). This is equivalent to the mITT (FAS). | Posted | Number | 95% Confidence Interval | Percentage of subjects | Stimulation day 1, 7-10 days after last FE 999049 or GONAL-F dose and 21-28 days after last FE 999049 or GONAL-F dose |
|
|
|
| Secondary | Proportion of Subjects With Late OHSS | Late OHSS was defined as OHSS with onset >9 days after triggering of final follicular maturation.The proportion of subjects with late OHSS, and late OHSS of moderate or severe grade are presented. | Safety analysis set (all randomised and exposed subjects). This is equivalent to the mITT (FAS). | Posted | Number | Percentage of subjects | >9 days after triggering of final follicular maturation |
|
|
|
|
| Secondary | Technical Malfunctions of the Administration Pen | Confirmed technical malfunction of administration pen. | Safety analysis set (all randomised and exposed subjects). This is equivalent to the mITT (FAS). | Posted | Number | Percentage of subjects | End-of-stimulation (up to 20 stimulation days) |
|
|
|
| 16 |
| 665 |
| 168 |
| 665 |
| EG001 | GONAL-F | GONAL-F was administered as single daily subcutaneous injections in the abdomen. The starting dose of GONAL-F was 150 IU and fixed for the first five stimulation days, after which it could be adjusted by 75 IU based on the individual response. The maximum allowed daily dose was 450 IU. Dosing continued until the criterion for triggering of final follicular maturation was met. Subjects could be treated for a maximum of 20 days. | 10 | 661 | 159 | 661 |
| Haemorrhage in pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 17.1 | Systematic Assessment |
|
| Abortion spontaneous | Pregnancy, puerperium and perinatal conditions | MedDRA 17.1 | Systematic Assessment |
|
| Biochemical pregnancy | Pregnancy, puerperium and perinatal conditions | MedDRA 17.1 | Systematic Assessment |
|
| Abortion threatened | Pregnancy, puerperium and perinatal conditions | MedDRA 17.1 | Systematic Assessment |
|
| Hyperemesis gravidarum | Pregnancy, puerperium and perinatal conditions | MedDRA 17.1 | Systematic Assessment |
|
| Affect lability | Psychiatric disorders | MedDRA 17.1 | Systematic Assessment |
|
| Colitis ulcerative | Gastrointestinal disorders | MedDRA 17.1 | Systematic Assessment |
|
| Ovarian hyperstimulation syndrome | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
|
| Adnexal torsion | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
|
| Post procedural infection | Infections and infestations | MedDRA 17.1 | Systematic Assessment |
|
| Headache | Nervous system disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pelvic pain | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
|
| Pelvic discomfort | Reproductive system and breast disorders | MedDRA 17.1 | Systematic Assessment |
|
The only disclosure restriction on the PI is that the sponsor can review the draft manuscript prior to publication and can request delay of publication where any contents are deemed patentable by the sponsor or confidential to the sponsor. Comments will be given within four weeks from receipt of the draft manuscript. Additional time may be required to allow Ferring to seek patent protection of the invention.
| Treatment comparison: <4 or >=20 oocytes retrieved | Likelihood ratio test | Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions. | =0.002 | Inclusion of treatment provides a better fit to the data. | Other | A logistic regression model was fitted to the data including AMH, log(AMH)2, treatment group and interactions between treatment group and AMH and treatment group and log(AMH)^2 in the linear predictor. A second logistic regression model (nested within the first model) was fitted including AMH and log(AMH)^2 in the linear predictor. |
| Any preventive intervention |
|
| Early OHSS (any grade) / preventive interventions |
|
| Early OHSS (mod/severe) / preventive interventions |
|
| Treatment comparison: Early OHSS (moderate/severe) | Likelihood ratio test | Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions. | =0.644 | Inclusion of treatment does not provide a better fit to the data. | Other | Nested logistic regression models were compared using the likelihood ratio test. The full logistic regression model included treatment as factor, log(AMH) as covariate and the interaction term. The nested model did not include treatment and the interaction term. |
| Treatment comparison: Preventive interventions | Likelihood ratio test | Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions. | =0.005 | Inclusion of treatment does not provide a better fit to the data. | Other | Nested logistic regression models were compared using the likelihood ratio test. The full logistic regression model included treatment as factor, log(AMH) as covariate and the interaction term. The nested model did not include treatment and the interaction term. |
| Treatment comparison: Early OHSS (any grade) and/or preventive interventions | Likelihood ratio test | Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions. | =0.046 | Inclusion of treatment does not provide a better fit to the data. | Other | Nested logistic regression models were compared using the likelihood ratio test. The full logistic regression model included treatment as factor, log(AMH) as covariate and the interaction term. The nested model did not include treatment and the interaction term. |
| Treatment comparison: Early OHSS (moderate/severe) and/or preventive interventions | Likelihood ratio test | Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions. | =0.019 | Inclusion of treatment does not provide a better fit to the data. | Other | Nested logistic regression models were compared using the likelihood ratio test. The full logistic regression model included treatment as factor, log(AMH) as covariate and the interaction term. The nested model did not include treatment and the interaction term. |
| Triggering with GnRH agonist |
|
|
Treatment comparison:Triggering with GnRH agonist |
| Likelihood ratio test |
| 0.019 |
P-value corresponds to test for treatment difference. |
| Odds Ratio (OR) |
| 0.42 |
| 2-Sided |
| 95 |
| 0.2 |
| 0.9 |
| Equivalence |
Treatment groups were compared using a logistic regression model with treatment and age (<35, 35-37, and 38-40 years) as factors. |
| Targeted response (8-14 oocytes) |
|
| Hyperresponse (15-19 oocytes) |
|
| Severe hyperresponse (≥ 20 oocytes) |
|
| van Elteren |
| =0.414 |
| Equivalence |
Treatment groups were compared using the van Elteren test adjusted for age (<35, 35-37, and 38-40 years). |
| van Elteren |
| = 0.58 |
| Equivalence |
Treatment groups were compared using the van Elteren test adjusted for age (<35, 35-37, and 38-40 years). |
| Treatment comparison: Late OHSS (moderate/severe) | Likelihood ratio test | Likelihood ratio test comparing the reduced model including only AMH to the full model including AMH, treatment group and interactions. | 0.390 | Inclusion of treatment does not provide a better fit to the data. | Other | Nested logistic regression models were compared using the likelihood ratio test. The full logistic regression model included treatment as factor, log(AMH) as covariate and the interaction term. The nested model did not include treatment and the interaction term. |