Infertility
Conditions
Brief summary
This study is aimed to demonstrate that highly purified Menotrophin produces significant lower progesterone serum levels during the follicular phase in comparison to Follitropin alpha in the treatment of subfertile females undergoing an in vitro fertilisation (IVF) and to investigate if the progesterone serum levels might be a useful predictor for the success rate of the ongoing pregnancy rates
Interventions
DRUGMenotrophin
Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met.
Starting on Day 2 or 3 of the menstrual cycle, 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met.
DRUGCetrorelix
Participants self-inject subcutaneously Cetrorelix in the morning at a daily dose of 0.25 mg/day from Day 5 of gonadotrophin administration on and continue throughout the period of gonadotrophin treatment up to day 12 as a maximum. The last dose of Cetrorelix is given on the day of ovulation induction.
DRUGChoriongonadotropin
10,000 IU administered by the Investigator or designated personnel in the evening of the day on which the hCG criterion is met (no later than Day 13). The criterion for hCG administration is three follicles \>+17 mm diameter as shown by pelvic ultrasound examination.
DRUGProgesterone
Vaginal gel progesterone is used once daily at a dose of 90 mg for a period of 30 days starting on the day of oocyte retrieval (approximately Day 14).
Sponsors
Ferring Arzneimittel GmbH
Ferring Pharmaceuticals
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
FEMALE
Age
34 Years to 42 Years
Healthy volunteers
No
Inclusion criteria
* Signed informed consent * Subfertile premenopausal female patients eligible for in vitro fertilisation (IVF) treatment * Aged ≥34 and ≤42 years * Body mass index of \>18 and \<28 kg/m\^2 * Normal pelvic ultrasound at Screening * No more than two previous gonadotrophin stimulated cycles of IVF or intracytoplasmic sperm injection (ICSI) in the history of infertility treatment (gonadotrophin stimulated cycles not used for IVF or ICSI do not count; Clomifen cycles are no exclusion criterion) * At least 3 consecutive ovulatory menstrual cycles of 24-35 days * No fertility stimulating drugs at all * Sperm of partner classified as normal according to World Health Organisation (WHO) 2010 criteria * Clinically normal baseline haematology, clinical chemistry, and urinalysis values * Negative serum Hepatitis B Surface Antigen (HBsAg), Hepatitis C Virus (HCV) and Human Immunodeficiency Virus (HIV) antibody tests within the last 6 months prior to Screening * Endocrine test results within the clinically normal limits at Screening
Exclusion criteria
* Presence of any clinically relevant systemic disease (e.g., insulin-dependent diabetes mellitus) * A history of or current endocrine disease (excluding treated hypothyreosis), including polycystic ovary syndrome (PCOS) and hyperprolactinaemia * A history of coagulation disorders * Persistent ovarian cysts (\>3 months) * A history of hypersensitivity to any of the constituents of the study medication or related compounds * Diagnosed poor (\<3 oocytes) responders to prior gonadotrophin stimulated ART-cycle * History of severe ovarian hyperstimulation syndrome in former gonadotrophin stimulated assisted reproductive technology (ART)-cycle
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration | approximately day 10 | Ovulation induction was performed by administration of hCG once three follicles \>=17 mm diameter as shown by pelvic ultrasound examination. This outcome compares the serum progesterone level the morning prior to hCG administration across treatment arm, and also by age stratum (\<39 years and \>=39 years). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Participants With Ongoing Pregnancy | approximately 3.5 months from study start (at least 9 weeks after first positive pregnancy test) | Ongoing pregnancy is defined as having a positive foetal heart action nine or more weeks after the first positive pregnancy test. |
| Number of Follicles at hCG Administration | approximately day 10 | Number of follicles \>=17 mm diameter detected by pelvic ultrasound examination at day of hCG administration. |
| Average Follicle Diameter at hCG Administration | approximately day 10 | — |
| Number of Cumulus-oocyte Complexes Retrieved | approximately day 12 after study start | Cumulus-oocyte complexes are oocytes with surrounding cumulus cells. |
| Number of Pronuclear Oocytes | approximately day 13 after study start | Pronuclear oocytes are fertilized oocytes. |
| Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | approximately day 13 | The count of participants with different quality grades of pronuclear stage oocytes is offered. Pronuclear stage oocytes are categorized into seven grades (0A, 0B, 1-5) representing different patterns of pronuclear morphology, according to the German Pronuclear Morphology Study Group. 0A is the highest quality oocyte and grade 5 is the lowest quality. Participants can have pronuclear stage oocytes of different grades and therefore are counted more than once. |
| Number of Embryos Transferred | approximately day 14 | Mean number of embryos transferred 2-3 days following oocyte retrieval. |
| Best Quality of an Embryo Transferred | approximately day 14 | Embryo quality was measured by the following grades: * Grade 1: Evenly sized cells, regular cleavage, no fragmentation * Grade 2: Regular or slightly irregular cleavage, \<=20% fragmentation * Grade 2.5: Regular or slightly irregular cleavage, \>20%and \<=50% fragmentation * Grade 3: Irregular cleavage, \>50% fragmentation, \>1 intact cell * Grade 4: Extensive fragmentation, only 1 cell intact * Grade 5: Totally fragmented, no viable cells. Grade 1 represents the healthiest embryos and Grade 5 embryos are not viable. |
| Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration | Day 7, approximately Day 10 (hCG Administration) | The influence of the progesterone level on the ongoing pregnancy rate (in relation to all randomized patients) was determined by means of the receiver operating characteristic (ROC) curve. Youden's Index (sensitivity + specificity -1) has a range of 0-1, with 0.5 indicating a random effect. |
| Endometrial Thickness on Day of hCG Administration | approximately day 10 | Endometrial thickness was assessed by pelvic ultrasound on the day of hCG administration. |
| Estradiol (E2) Levels on Day of hCG Administration | approximately day 10 | — |
| Percentage of Participants With Successful Embryo Transfer | approximately day 18 | — |
| Number of Days Stimulated With Gonadotrophins | Day 1 up to Day 12 | Number of days in which gonadotrophins were administered until hCG criteria were met. If hCG criteria were not met by day 13, the participant was withdrawn from the study. |
| Number of Ampoules of Gonadotrophins Used | Day 1 up to Day 12 | Number of ampoules of gonadotrophins used with the goal of reaching hCG criteria. Each ampoule contained 75 IU of either menotrophin or follitrophin alpha. |
| Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test | approximately 2.5 months from start of study, 6 weeks after first positive pregnancy test | A pelvic ultrasound scan was performed approximately 6 weeks after the first positive pregnancy test and the presence of an active foetal heart action indicated a clinical pregnancy. |
| Summary of Pregnancy Outcome | up to 10 months | Pregnancy outcomes were reported at the optional long-term follow up visit. |
| Number of Frozen Oocytes at Pronuclear Stage | approximately day 14 | No more than three normally developed embryos were transferred 2-3 days after oocyte retrieval. Other normally developed embryos were frozen. |
Countries
Germany
Participant flow
Pre-assignment details
One hundred seventy patients were screened.
Participants by arm
| Arm | Count |
|---|---|
| Menotrophin Menotrophin 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. | 62 |
| Follitrophin Alpha Follitrophin alpha 150 IU (up to 300 IU) by subcutaneous injection once per day in the morning for up to 12 days until human chorionic gonadotropin (hCG) criteria are met. Pituitary down-regulation (cetrorelix), ovulation induction (choriongonadotropin), and luteal phase support (intravaginal progesterone) are administered the same way in both treatment arms. | 62 |
| Total | 124 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 2 | 1 |
| Overall Study | Completed protocol | 2 | 1 |
| Overall Study | Did not meet hCG criterion | 2 | 0 |
| Overall Study | Other | 1 | 1 |
Baseline characteristics
| Characteristic | Menotrophin | Follitrophin Alpha | Total |
|---|---|---|---|
| Aetiology of Infertility Endometriosis | 4 participants | 3 participants | 7 participants |
| Aetiology of Infertility Idiopathic | 36 participants | 33 participants | 69 participants |
| Aetiology of Infertility Missing values | 1 participants | 0 participants | 1 participants |
| Aetiology of Infertility Other | 1 participants | 8 participants | 9 participants |
| Aetiology of Infertility Tubal factor | 20 participants | 18 participants | 38 participants |
| Age, Continuous | 36.5 years STANDARD_DEVIATION 2.4 | 36.7 years STANDARD_DEVIATION 2.3 | 36.6 years STANDARD_DEVIATION 2.4 |
| Age, Customized < 39 years | 50 participants | 49 participants | 99 participants |
| Age, Customized >=39 years | 12 participants | 13 participants | 25 participants |
| Duration of Infertility | 45.7 months STANDARD_DEVIATION 35 | 40.6 months STANDARD_DEVIATION 25.6 | 43.2 months STANDARD_DEVIATION 30.7 |
| Former Treatment for Infertility No | 24 participants | 24 participants | 48 participants |
| Former Treatment for Infertility Yes | 38 participants | 38 participants | 76 participants |
| Length of Menstrual Cycle | 28.3 days STANDARD_DEVIATION 1.7 | 28.2 days STANDARD_DEVIATION 1.5 | 28.2 days STANDARD_DEVIATION 1.6 |
| Menstrual Cycle Irregular | 0 participants | 0 participants | 0 participants |
| Menstrual Cycle Regular | 62 participants | 62 participants | 124 participants |
| Participants with Gonadotrophin Stimulated Assisted Reproductive Technology (ART) Cycle Missing Values | 49 participants | 44 participants | 93 participants |
| Participants with Gonadotrophin Stimulated Assisted Reproductive Technology (ART) Cycle No | 0 participants | 0 participants | 0 participants |
| Participants with Gonadotrophin Stimulated Assisted Reproductive Technology (ART) Cycle Yes | 13 participants | 18 participants | 31 participants |
| Sex: Female, Male Female | 62 Participants | 62 Participants | 124 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
| Weight | 64.3 kg STANDARD_DEVIATION 8.2 | 63.5 kg STANDARD_DEVIATION 8.7 | 63.9 kg STANDARD_DEVIATION 8.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 43 / 62 | 45 / 62 |
| serious Total, serious adverse events | 2 / 62 | 0 / 62 |
Outcome results
Primary
Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration
Ovulation induction was performed by administration of hCG once three follicles \>=17 mm diameter as shown by pelvic ultrasound examination. This outcome compares the serum progesterone level the morning prior to hCG administration across treatment arm, and also by age stratum (\<39 years and \>=39 years).
Time frame: approximately day 10
Population: Full analysis set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration | 0.69 ng/ml | Standard Deviation 0.34 |
| Menotrophin: Stratum Age <39 Yrs | Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration | 0.72 ng/ml | Standard Deviation 0.35 |
| Menotrophin: Stratum Age >=39 Yrs | Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration | 0.54 ng/ml | Standard Deviation 0.25 |
| Follitrophin Alpha | Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration | 0.89 ng/ml | Standard Deviation 0.41 |
| Follitrophin Alpha: Stratum Age <39 Yrs | Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration | 0.92 ng/ml | Standard Deviation 0.43 |
| Follitrophin Alpha: Stratum Age >=39 Yrs | Serum Progesterone (P4) Level in the Morning of the Day of Human Chorionic Gonadotrophin (hCG) Administration | 0.80 ng/ml | Standard Deviation 0.28 |
p-value: 0.003t-test, 2 sided
Comparison: Age \< 39 yearsp-value: 0.015t-test, 2 sided
Comparison: Age \>= 39 yearsp-value: 0.027t-test, 2 sided
Secondary
Average Follicle Diameter at hCG Administration
Time frame: approximately day 10
Population: The per-protocol (PP) set of participants with non-missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Average Follicle Diameter at hCG Administration | 17.6 mm | Standard Deviation 1.8 |
| Menotrophin: Stratum Age <39 Yrs | Average Follicle Diameter at hCG Administration | 18.1 mm | Standard Deviation 1.2 |
p-value: 0.121t-test, 2 sided
Secondary
Best Quality of an Embryo Transferred
Embryo quality was measured by the following grades: * Grade 1: Evenly sized cells, regular cleavage, no fragmentation * Grade 2: Regular or slightly irregular cleavage, \<=20% fragmentation * Grade 2.5: Regular or slightly irregular cleavage, \>20%and \<=50% fragmentation * Grade 3: Irregular cleavage, \>50% fragmentation, \>1 intact cell * Grade 4: Extensive fragmentation, only 1 cell intact * Grade 5: Totally fragmented, no viable cells. Grade 1 represents the healthiest embryos and Grade 5 embryos are not viable.
Time frame: approximately day 14
Population: Per protocol set of participants who had embryos transferred
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Menotrophin | Best Quality of an Embryo Transferred | Grade 1 | 22 participants |
| Menotrophin | Best Quality of an Embryo Transferred | Grade 2 | 18 participants |
| Menotrophin | Best Quality of an Embryo Transferred | Grade >2 | 6 participants |
| Menotrophin: Stratum Age <39 Yrs | Best Quality of an Embryo Transferred | Grade 1 | 26 participants |
| Menotrophin: Stratum Age <39 Yrs | Best Quality of an Embryo Transferred | Grade 2 | 22 participants |
| Menotrophin: Stratum Age <39 Yrs | Best Quality of an Embryo Transferred | Grade >2 | 6 participants |
p-value: 0.871Chi-squared
Secondary
Endometrial Thickness on Day of hCG Administration
Endometrial thickness was assessed by pelvic ultrasound on the day of hCG administration.
Time frame: approximately day 10
Population: Per protocol set of participants. One participant in the Follitrophin Alpha arm was missing a measurement.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Endometrial Thickness on Day of hCG Administration | 10.8 mm | Standard Deviation 2.1 |
| Menotrophin: Stratum Age <39 Yrs | Endometrial Thickness on Day of hCG Administration | 11.0 mm | Standard Deviation 2.2 |
p-value: 0.62t-test, 2 sided
Secondary
Estradiol (E2) Levels on Day of hCG Administration
Time frame: approximately day 10
Population: Per protocol set. Five participants from each treatment arm were missing blood samples.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Estradiol (E2) Levels on Day of hCG Administration | 1.81 ng/ml | Standard Deviation 1.21 |
| Menotrophin: Stratum Age <39 Yrs | Estradiol (E2) Levels on Day of hCG Administration | 1.65 ng/ml | Standard Deviation 0.87 |
p-value: 0.478t-test, 2 sided
Secondary
Number of Ampoules of Gonadotrophins Used
Number of ampoules of gonadotrophins used with the goal of reaching hCG criteria. Each ampoule contained 75 IU of either menotrophin or follitrophin alpha.
Time frame: Day 1 up to Day 12
Population: Per protocol set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Number of Ampoules of Gonadotrophins Used | 20.8 ampoules | Standard Deviation 7.5 |
| Menotrophin: Stratum Age <39 Yrs | Number of Ampoules of Gonadotrophins Used | 21.5 ampoules | Standard Deviation 6.8 |
p-value: 0.405Wilcoxon (Mann-Whitney)
Secondary
Number of Cumulus-oocyte Complexes Retrieved
Cumulus-oocyte complexes are oocytes with surrounding cumulus cells.
Time frame: approximately day 12 after study start
Population: The per-protocol (PP) set of participants with non-missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Number of Cumulus-oocyte Complexes Retrieved | 6.8 oocytes | Standard Deviation 4.2 |
| Menotrophin: Stratum Age <39 Yrs | Number of Cumulus-oocyte Complexes Retrieved | 10.0 oocytes | Standard Deviation 4.6 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Number of Days Stimulated With Gonadotrophins
Number of days in which gonadotrophins were administered until hCG criteria were met. If hCG criteria were not met by day 13, the participant was withdrawn from the study.
Time frame: Day 1 up to Day 12
Population: Per protocol set
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Number of Days Stimulated With Gonadotrophins | 8.7 days | Standard Deviation 1.9 |
| Menotrophin: Stratum Age <39 Yrs | Number of Days Stimulated With Gonadotrophins | 9.1 days | Standard Deviation 1.6 |
p-value: 0.295Wilcoxon (Mann-Whitney)
Secondary
Number of Embryos Transferred
Mean number of embryos transferred 2-3 days following oocyte retrieval.
Time frame: approximately day 14
Population: The per-protocol (PP) set who had embryos transferred. PP set is defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Number of Embryos Transferred | 2.0 embryos | Standard Deviation 0.5 |
| Menotrophin: Stratum Age <39 Yrs | Number of Embryos Transferred | 2.0 embryos | Standard Deviation 0.4 |
p-value: 0.482Wilcoxon (Mann-Whitney)
Secondary
Number of Follicles at hCG Administration
Number of follicles \>=17 mm diameter detected by pelvic ultrasound examination at day of hCG administration.
Time frame: approximately day 10
Population: The per-protocol (PP) set of participants with non-missing values. PP set is defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Number of Follicles at hCG Administration | 8.7 follicles | Standard Deviation 4.7 |
| Menotrophin: Stratum Age <39 Yrs | Number of Follicles at hCG Administration | 10.5 follicles | Standard Deviation 4.1 |
p-value: 0.004Wilcoxon (Mann-Whitney)
Secondary
Number of Frozen Oocytes at Pronuclear Stage
No more than three normally developed embryos were transferred 2-3 days after oocyte retrieval. Other normally developed embryos were frozen.
Time frame: approximately day 14
Population: Per protocol set of participants who had embryos transferred
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Number of Frozen Oocytes at Pronuclear Stage | 1.0 oocytes | Standard Deviation 2.2 |
| Menotrophin: Stratum Age <39 Yrs | Number of Frozen Oocytes at Pronuclear Stage | 2.7 oocytes | Standard Deviation 2.9 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade
The count of participants with different quality grades of pronuclear stage oocytes is offered. Pronuclear stage oocytes are categorized into seven grades (0A, 0B, 1-5) representing different patterns of pronuclear morphology, according to the German Pronuclear Morphology Study Group. 0A is the highest quality oocyte and grade 5 is the lowest quality. Participants can have pronuclear stage oocytes of different grades and therefore are counted more than once.
Time frame: approximately day 13
Population: The per-protocol (PP) set -- defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Menotrophin | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 1 | 33 participants |
| Menotrophin | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 3 | 8 participants |
| Menotrophin | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 0B | 15 participants |
| Menotrophin | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 4 | 2 participants |
| Menotrophin | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 2 | 15 participants |
| Menotrophin | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 5 | 11 participants |
| Menotrophin | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 0A | 11 participants |
| Menotrophin: Stratum Age <39 Yrs | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 5 | 23 participants |
| Menotrophin: Stratum Age <39 Yrs | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 0A | 17 participants |
| Menotrophin: Stratum Age <39 Yrs | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 0B | 23 participants |
| Menotrophin: Stratum Age <39 Yrs | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 1 | 40 participants |
| Menotrophin: Stratum Age <39 Yrs | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 2 | 25 participants |
| Menotrophin: Stratum Age <39 Yrs | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 3 | 24 participants |
| Menotrophin: Stratum Age <39 Yrs | Number of Participants With Pronuclear Stage Oocytes at Each Quality Grade | Grade 4 | 11 participants |
Secondary
Number of Pronuclear Oocytes
Pronuclear oocytes are fertilized oocytes.
Time frame: approximately day 13 after study start
Population: The per-protocol (PP) set of participants with non-missing values.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Menotrophin | Number of Pronuclear Oocytes | 3.7 oocytes | Standard Deviation 2.8 |
| Menotrophin: Stratum Age <39 Yrs | Number of Pronuclear Oocytes | 5.9 oocytes | Standard Deviation 3.7 |
p-value: <0.001Wilcoxon (Mann-Whitney)
Secondary
Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test
A pelvic ultrasound scan was performed approximately 6 weeks after the first positive pregnancy test and the presence of an active foetal heart action indicated a clinical pregnancy.
Time frame: approximately 2.5 months from start of study, 6 weeks after first positive pregnancy test
Population: Per protocol set
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Menotrophin | Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test | 29.2 percentage of participants |
| Menotrophin: Stratum Age <39 Yrs | Percentage of Participants With Clinical Pregnancy 6 Weeks After the First Positive Pregnancy Test | 31.0 percentage of participants |
p-value: 1Fisher Exact
Secondary
Percentage of Participants With Ongoing Pregnancy
Ongoing pregnancy is defined as having a positive foetal heart action nine or more weeks after the first positive pregnancy test.
Time frame: approximately 3.5 months from study start (at least 9 weeks after first positive pregnancy test)
Population: The per-protocol (PP) set -- defined as participants of the full analysis set without any major protocol violation (i.e., any deviation which was likely to bias the assessment of the primary endpoint).
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Menotrophin | Percentage of Participants With Ongoing Pregnancy | 29.2 percentage of participants |
| Menotrophin: Stratum Age <39 Yrs | Percentage of Participants With Ongoing Pregnancy | 31.0 percentage of participants |
p-value: 1Fisher Exact
Secondary
Percentage of Participants With Successful Embryo Transfer
Time frame: approximately day 18
Population: Per protocol set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Menotrophin | Percentage of Participants With Successful Embryo Transfer | No | 4.2 percentage of participants |
| Menotrophin | Percentage of Participants With Successful Embryo Transfer | Yes | 95.8 percentage of participants |
| Menotrophin: Stratum Age <39 Yrs | Percentage of Participants With Successful Embryo Transfer | No | 6.9 percentage of participants |
| Menotrophin: Stratum Age <39 Yrs | Percentage of Participants With Successful Embryo Transfer | Yes | 93.1 percentage of participants |
p-value: 0.69Fisher Exact
Secondary
Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration
The influence of the progesterone level on the ongoing pregnancy rate (in relation to all randomized patients) was determined by means of the receiver operating characteristic (ROC) curve. Youden's Index (sensitivity + specificity -1) has a range of 0-1, with 0.5 indicating a random effect.
Time frame: Day 7, approximately Day 10 (hCG Administration)
Population: Full analysis set
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Menotrophin | Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration | Day 7 | 0.5189 Youden's index |
| Menotrophin | Receiver Operating Characteristic (ROC) Analysis of Progesterone as Predictor for Ongoing Pregnancy Rate at Day 7 and Day of hCG Administration | Day of hCG Administration (approx Day 10) | 0.4944 Youden's index |
Secondary
Summary of Pregnancy Outcome
Pregnancy outcomes were reported at the optional long-term follow up visit.
Time frame: up to 10 months
Population: Per protocol set of participants who reported information during the optional long-term follow up visit.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Menotrophin | Summary of Pregnancy Outcome | Live birth | 13 participants |
| Menotrophin | Summary of Pregnancy Outcome | Ectopic pregnancy | 1 participants |
| Menotrophin | Summary of Pregnancy Outcome | Congenial abnormality | 0 participants |
| Menotrophin: Stratum Age <39 Yrs | Summary of Pregnancy Outcome | Live birth | 16 participants |
| Menotrophin: Stratum Age <39 Yrs | Summary of Pregnancy Outcome | Ectopic pregnancy | 0 participants |
| Menotrophin: Stratum Age <39 Yrs | Summary of Pregnancy Outcome | Congenial abnormality | 1 participants |