Progesterone Supplementation in Women Undergoing ART
Conditions
Keywords
Progesterone vaginal ring (PVR), Vaginal progesterone ring, Assisted reproductive technology (ART), Infertility
Brief summary
The purpose of the study is to assess the safety of Progesterone Vaginal Ring (PVR) in women undergoing fresh embryo transfer (ART).
Interventions
A flexible, non-degradable PVR containing progesterone in micronized formulation and dispersed evenly throughout the ring.
Sponsors
Ferring Pharmaceuticals
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Masking description
Open-label trial
Eligibility
Sex/Gender
FEMALE
Age
18 Years to 34 Years
Healthy volunteers
No
Inclusion criteria
* Pre-menopausal women aged 18-34 at the time of consent. * Documentation of a normal uterine cavity by hysteroscopy, hydrosonogram, or hysterosalpingogram within one year of screening. * Normal Pap smear test within 24 months of screening. * At least one cycle without reproductive hormone medication prior to screening follicle-stimulating hormone (FSH) and estradiol blood draw. * Tubal, idiopathic, male factor, ovulatory dysfunction, or endometriosis-linked infertility.
Exclusion criteria
* Body mass index greater than 38 kg/m\^2. * FSH greater than 15 IU/L during the early follicular phase (Day 2-4). For those participants with polycystic ovarian syndrome, a Day 2-4 FSH level can be obtained following a progestogen withdrawal or spontaneous menses. * Clinically significant gynecologic pathology, such as submucosal fibroids, intramural fibroids \>5 cm, communicating hydrosalpinx, uncorrected uterine septum, endometrial cancer or endometrial atypia, scar tissue inside the cavity or poorly developed uterine lining from prior uterine surgery, pelvic tuberculosis, or any other conditions that could adversely affect pregnancy success. * Uncontrolled elevation of prolactin or too little thyroid hormone in the blood. * History of more than one failed fresh in vitro fertilization cycle. A failed cycle is defined as having started a cycle and not becoming pregnant or pregnancy loss prior to the 20th week of pregnancy.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Rate of Spontaneous Abortions Occurring on or Before 12 Weeks Post-oocyte Retrieval | On or before 12 weeks post-oocyte retrieval | Frequency of participants with spontaneous abortions on or before 12 weeks post-oocyte retrieval and undergoing fresh embryo transfer was presented. Spontaneous abortion was defined as two positive beta-human chorionic gonadotropin (β-hCG) tests occurring at least two days apart on or after 2 weeks post-oocyte retrieval, but followed by observation of any empty intrauterine gestational sac (blighted ovum), intrauterine gestation without a fetal heart beat, or absence of viable fetuses, as documented by transvaginal ultrasound (TVUS). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Cumulative Rate of Spontaneous Abortions Occurring at 10 Weeks Post-oocyte Retrieval | At 10 weeks post-oocyte retrieval | Frequency of participants with spontaneous abortions at 10 weeks post-oocyte retrieval was presented. |
| Cumulative Rate of Biochemical Abortion Within 6 Weeks Post-oocyte Retrieval | Within 6 weeks post-oocyte retrieval | Frequency of participants with biochemical abortions within 6 weeks post-oocyte retrieval was presented. Biochemical abortion was defined as a positive β-hCG test at 2 weeks and 2 weeks +3-4 days post-oocyte retrieval, but followed by no observed gestational sac on a later TVUS, or followed by a negative β-hCG test. |
| Cumulative Rate of Biochemical Abortion Within 10 Weeks Post-oocyte Retrieval | Within 10 weeks post-oocyte retrieval | Frequency of participants with biochemical abortions within 10 weeks post-oocyte retrieval was presented. |
| Positive β-hCG Rate at 2 Weeks and 2 Weeks +3-4 Days Post Oocyte Retrieval | At 2 weeks and 2 weeks +3-4 Days post oocyte retrieval | Frequency of participants with positive β-hCG rate at 2 weeks and 2 weeks +3-4 Days was presented. Positive β-hCG was defined as a positive serum β-hCG test at 2 weeks and 2 weeks +3-4 Days post-oocyte retrieval. |
| Clinical Pregnancy Rate at 6 Weeks | At 6 weeks post-oocyte retrieval | Frequency of participants with clinical pregnancy at 6 weeks was presented. Clinical pregnancy was defined as a TVUS showing at least 1 intrauterine gestational sac with fetal heart-beat at 6 weeks post-oocyte retrieval. |
| Clinical Pregnancy Rate at 10 Weeks | At 10 weeks post-oocyte retrieval | Frequency of participants with clinical pregnancy at 10 weeks was presented. |
| Rate of Ectopic and Heterotopic Pregnancies Following Oocyte Retrieval | At 4 weeks +3-4 Days after oocyte retrieval | Frequency of participants with ectopic and heterotopic pregnancies was presented. |
| Rate of Abnormal Findings in Clinical Laboratory Tests (Clinical Chemistry, Hematology, and Urinalysis) | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | Participants with at least one abnormal finding in clinical laboratory tests (i.e. abnormal clinical significant \[CS\] values: as assessed by investigator) were reported. Clinical chemistry included: glucose, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, potassium, sodium, chloride, calcium, estimated glomerular filtration rate, and gamma-glutamyl transferase; hematology included: basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, erythrocytes, and leukocytes; urinalysis included: specific gravity, ketones, pH, protein, blood, and glucose. |
| Rate of Abnormal Findings in Vital Signs | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | Participants with at least one abnormal finding (i.e. abnormal CS values: as assessed by investigator) in vital signs were reported. Vital signs includes: Weight (kg): decrease of \>=7% from baseline (BL) or increase of \>=7% from BL; Systolic Blood Pressure (SBP): \<=90 mmHg and decrease of \>=20 mmHg from BL or \>=180 mmHg and increase of \>= 20 mmHg from BL; Diastolic Blood Pressure (DBP): \<= 50 mmHg and decrease of \>= 15 mmHg from BL or \>=105 mmHg and increase of \>=15 mmHg from BL; Heart Rate: \<=50 (beats per minute \[bpm\]) and decrease of \>= 15 bpm from BL or \>=120 bpm and increase of \>=15 from BL; Temperature \>= 38.3 degree Celsius. |
| Cumulative Rate of Spontaneous Abortions Occurring at 6 Weeks Post-oocyte Retrieval | At 6 weeks post-oocyte retrieval | Frequency of participants with spontaneous abortions at 6 weeks post-oocyte retrieval was presented. |
| Frequency and Intensity/Grade of Vaginal Bleeding/Spotting | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | Frequency of participants with vaginal bleeding/spotting was presented in total and by categories of intensity/grade (mild, moderate and severe). Vaginal bleeding was recorded in a bleeding log by the participant. The severity of the bleeding was determined using a Pictorial Blood Loss Assessment chart. |
| Frequency and Intensity/Grade of Vaginal Hemorrhage | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | Frequency of participants with vaginal hemorrhage was presented in total and by categories of intensity/grade (mild, moderate and severe). Vaginal hemorrhage was defined as a) blood loss of greater than 500 mL based on the opinion of the Investigator or b) hemoglobin post-treatment lesser than 10 gm/dL or c) blood loss requiring transfusion. |
| Frequency and Intensity/Grade of Vaginal Pain | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | The frequency of participants with vaginal pain was presented in total and by categories of intensity/grade. The intensity of vaginal pain was evaluated as symptoms score of pain and dyspareunia (pain with sexual activity) as: Grade 1 (mild) - Pain causing no or minimal inference with usual social & functional activities; Grade 2 (moderate) - Pain causing greater than minimal inference with usual social & functional activities or the need for non-narcotic medication; Grade 3 (severe) - Pain causing inability to perform usual social & functional activities or the need for narcotic medication; Grade 4 (potentially life threatening) - Disabling pain causing inability to perform basic self-care functions OR hospitalization (other than emergency room visit) indicated. Dyspareunia (pain with sexual activity): Grade 1 (mild) - Pain causing no or minimal inference with sexual function; Grade 2 (moderate) - Pain causing greater than minimal inference with sexual function. |
| Frequency and Intensity/Grade of Vaginal Infection | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | Frequency of participants with vaginal infection was presented in total and by categories of intensity/grade (mild, moderate and severe). |
| Frequency and Intensity/Grade of Vaginal Irritation | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | The frequency of participants with vaginal irritation was presented in total and by categories of intensity/grade. The intensity of vaginal irritation evaluated as symptoms score of vaginal itching, vaginal dryness, and vaginal discharge. Vaginal itching: Grade 1 (mild)-itching causing no, mild or moderate inference with usual social & functional activities; Grade 2 (moderate)-itching causing inability to perform usual social & functional activities; may require intervention such as antihistamine or bathing. Vaginal dryness: Grade 1 (mild)-dryness causing no or minimal inference with usual sexual, social & functional activities; Grade 2 (moderate)-dryness causing greater than minimal inference with usual sexual, social & functional activities. Vaginal discharge by participant report: Grade 1 (mild)-mild-moderate increase in amount above participant BL-no sanitary protection required; Grade 2 (moderate)-profuse increase in discharge requiring pad use or other hygienic intervention. |
| Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | Frequency of participants with AEs associated with vaginal and cervical abrasions and lesions, by intensity, seriousness, & relatedness was presented. Intensity was evaluated as symptoms score: Vaginal/cervical lesions:Grade 0 (Normal)- Normal variants including skin tags, moles, scars, etc; Grade 1 (mild) - Blisters, ulcerations, or pustules, no treatment indicated; Grade 2 (moderate)- Blisters, ulcerations, or pustules with treatment indicated; Grade 3 (severe) - Severe epithelial disruption requiring hospitalization; Vaginal/cervical abrasions: Grade 0 (Normal) - None; Grade 1 (mild)- Superficial disruptions and disruptions extending through the mucosa with minimal impact on life; Grade 2 (moderate)- Large disruptions extending through the mucosa or large superficial disruptions, hospitalization not indicated; Grade 3 (severe)- Large disruptions extending through the mucosa or large superficial disruptions, hospitalization indicated. Relatedness to IMP was assessed by investigator. |
| Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal Adhesions | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | The frequency of participants with AEs associated with vaginal adhesion (total), by categories of intensity, seriousness, and relatedness was presented. The intensity was evaluated as symptoms score of vaginal adhesion as: Grade 0 (Normal) - None; Grade 1 (mild) - asymptomatic, manual removal of ring possible; Grade 2 (moderate) - Symptomatic (eg: irritation reported by participant), manual removal of ring possible; Grade 3 (severe) - Surgical intervention (eg: adhesiolysis) required to resolve; Grade 4 (potentially life threatening) - urgent intervention indicated. The AEs associated with vaginal adhesion of Grade 4 intensity were considered to be serious. Relatedness to IMP was assessed by investigator. |
| Frequency and Reason for PVR Discontinuation | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | Frequency of participants who prematurely discontinued PVR (i.e. did not fulfill 10 weeks of PVR treatment) was presented by reason. |
| Frequency, Intensity/Grade, Seriousness, and Relatedness of Adverse Events (AEs) | From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval) | The frequency of participants with total AEs, AEs by categories of intensity (mild, moderate, severe), seriousness and relatedness was presented. An AE is any untoward medical occurrence in a participant participating in a clinical trial. The intensity of an AE was classified using the following 3-point scale: mild=awareness of signs or symptoms, but no disruption of usual activity; moderate=event sufficient to affect usual activity (disturbing); or severe= inability to work or perform usual activities (unacceptable). Seriousness refers to death, hospitalization/ prolongation of existing hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly. The possibility of whether the IMP caused the AE would be classified as: reasonable possibility, no reasonable possibility. All the reasonable possible causality to the IMP were referred to as adverse drug reactions (ADRs). Relatedness of AEs to IMP was assessed by the investigator. |
Countries
United States
Participant flow
Recruitment details
The trial was conducted at 14 trial centers in the United States (US) between 26 July 2018 to 29 July 2019.
Pre-assignment details
In total 352 participants were screened. Of these, 98 were screening failures and 254 participants were treated with investigational medicinal product (IMP), progesterone vaginal ring (PVR).
Participants by arm
| Arm | Count |
|---|---|
| Progesterone Vaginal Ring Treatment started on the day following oocyte retrieval and could be continued through Week 12 of pregnancy (10 weeks post-oocyte retrieval), depending on the participants pregnancy assessment. A new PVR was inserted every 7 days with up to 10 PVRs used. | 254 |
| Total | 254 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 44 |
| Overall Study | Lost to Follow-up | 1 |
| Overall Study | Personal issues | 1 |
| Overall Study | Withdrawal by Subject | 2 |
Baseline characteristics
| Characteristic | Progesterone Vaginal Ring |
|---|---|
| Age, Continuous | 30.8 years STANDARD_DEVIATION 2.72 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 30 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 224 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 3 Participants |
| Race (NIH/OMB) Asian | 22 Participants |
| Race (NIH/OMB) Black or African American | 17 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 2 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 210 Participants |
| Sex: Female, Male Female | 254 Participants |
| Sex: Female, Male Male | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 254 |
| other Total, other adverse events | 72 / 254 |
| serious Total, serious adverse events | 4 / 254 |
Outcome results
Primary
Cumulative Rate of Spontaneous Abortions Occurring on or Before 12 Weeks Post-oocyte Retrieval
Frequency of participants with spontaneous abortions on or before 12 weeks post-oocyte retrieval and undergoing fresh embryo transfer was presented. Spontaneous abortion was defined as two positive beta-human chorionic gonadotropin (β-hCG) tests occurring at least two days apart on or after 2 weeks post-oocyte retrieval, but followed by observation of any empty intrauterine gestational sac (blighted ovum), intrauterine gestation without a fetal heart beat, or absence of viable fetuses, as documented by transvaginal ultrasound (TVUS).
Time frame: On or before 12 weeks post-oocyte retrieval
Population: The mITT analysis set consisted of all participants who had successful oocyte retrieval, received at least 1 dose of IMP, and had completed fresh embryo transfer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone Vaginal Ring | Cumulative Rate of Spontaneous Abortions Occurring on or Before 12 Weeks Post-oocyte Retrieval | 7.4 percentage of participants |
Secondary
Clinical Pregnancy Rate at 10 Weeks
Frequency of participants with clinical pregnancy at 10 weeks was presented.
Time frame: At 10 weeks post-oocyte retrieval
Population: The mITT analysis set consisted of all participants who had successful oocyte retrieval, received at least 1 dose of IMP, and had completed fresh embryo transfer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone Vaginal Ring | Clinical Pregnancy Rate at 10 Weeks | 43.2 percentage of participants |
Secondary
Clinical Pregnancy Rate at 6 Weeks
Frequency of participants with clinical pregnancy at 6 weeks was presented. Clinical pregnancy was defined as a TVUS showing at least 1 intrauterine gestational sac with fetal heart-beat at 6 weeks post-oocyte retrieval.
Time frame: At 6 weeks post-oocyte retrieval
Population: The mITT analysis set consisted of all participants who had successful oocyte retrieval, received at least 1 dose of IMP, and had completed fresh embryo transfer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone Vaginal Ring | Clinical Pregnancy Rate at 6 Weeks | 44.9 percentage of participants |
Secondary
Cumulative Rate of Biochemical Abortion Within 10 Weeks Post-oocyte Retrieval
Frequency of participants with biochemical abortions within 10 weeks post-oocyte retrieval was presented.
Time frame: Within 10 weeks post-oocyte retrieval
Population: The mITT analysis set consisted of all participants who had successful oocyte retrieval, received at least 1 dose of IMP, and had completed fresh embryo transfer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone Vaginal Ring | Cumulative Rate of Biochemical Abortion Within 10 Weeks Post-oocyte Retrieval | 10.3 percentage of participants |
Secondary
Cumulative Rate of Biochemical Abortion Within 6 Weeks Post-oocyte Retrieval
Frequency of participants with biochemical abortions within 6 weeks post-oocyte retrieval was presented. Biochemical abortion was defined as a positive β-hCG test at 2 weeks and 2 weeks +3-4 days post-oocyte retrieval, but followed by no observed gestational sac on a later TVUS, or followed by a negative β-hCG test.
Time frame: Within 6 weeks post-oocyte retrieval
Population: The mITT analysis set consisted of all participants who had successful oocyte retrieval, received at least 1 dose of IMP, and had completed fresh embryo transfer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone Vaginal Ring | Cumulative Rate of Biochemical Abortion Within 6 Weeks Post-oocyte Retrieval | 10.3 percentage of participants |
Secondary
Cumulative Rate of Spontaneous Abortions Occurring at 10 Weeks Post-oocyte Retrieval
Frequency of participants with spontaneous abortions at 10 weeks post-oocyte retrieval was presented.
Time frame: At 10 weeks post-oocyte retrieval
Population: The mITT analysis set consisted of all participants who had successful oocyte retrieval, received at least 1 dose of IMP, and had completed fresh embryo transfer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone Vaginal Ring | Cumulative Rate of Spontaneous Abortions Occurring at 10 Weeks Post-oocyte Retrieval | 7.4 percentage of participants |
Secondary
Cumulative Rate of Spontaneous Abortions Occurring at 6 Weeks Post-oocyte Retrieval
Frequency of participants with spontaneous abortions at 6 weeks post-oocyte retrieval was presented.
Time frame: At 6 weeks post-oocyte retrieval
Population: The mITT analysis set consisted of all participants who had successful oocyte retrieval, received at least 1 dose of IMP, and had completed fresh embryo transfer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone Vaginal Ring | Cumulative Rate of Spontaneous Abortions Occurring at 6 Weeks Post-oocyte Retrieval | 5.8 percentage of participants |
Secondary
Frequency and Intensity/Grade of Vaginal Bleeding/Spotting
Frequency of participants with vaginal bleeding/spotting was presented in total and by categories of intensity/grade (mild, moderate and severe). Vaginal bleeding was recorded in a bleeding log by the participant. The severity of the bleeding was determined using a Pictorial Blood Loss Assessment chart.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Bleeding/Spotting | Any vaginal bleeding | 4 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Bleeding/Spotting | Mild vaginal bleeding | 3 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Bleeding/Spotting | Moderate vaginal bleeding | 1 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Bleeding/Spotting | Severe vaginal bleeding | 1 participants |
Secondary
Frequency and Intensity/Grade of Vaginal Hemorrhage
Frequency of participants with vaginal hemorrhage was presented in total and by categories of intensity/grade (mild, moderate and severe). Vaginal hemorrhage was defined as a) blood loss of greater than 500 mL based on the opinion of the Investigator or b) hemoglobin post-treatment lesser than 10 gm/dL or c) blood loss requiring transfusion.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Hemorrhage | 0 participants |
Secondary
Frequency and Intensity/Grade of Vaginal Infection
Frequency of participants with vaginal infection was presented in total and by categories of intensity/grade (mild, moderate and severe).
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Infection | Mild vaginal infection | 3 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Infection | Moderate vaginal infection | 1 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Infection | Severe vaginal infection | 0 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Infection | Any vaginal infection | 4 participants |
Secondary
Frequency and Intensity/Grade of Vaginal Irritation
The frequency of participants with vaginal irritation was presented in total and by categories of intensity/grade. The intensity of vaginal irritation evaluated as symptoms score of vaginal itching, vaginal dryness, and vaginal discharge. Vaginal itching: Grade 1 (mild)-itching causing no, mild or moderate inference with usual social & functional activities; Grade 2 (moderate)-itching causing inability to perform usual social & functional activities; may require intervention such as antihistamine or bathing. Vaginal dryness: Grade 1 (mild)-dryness causing no or minimal inference with usual sexual, social & functional activities; Grade 2 (moderate)-dryness causing greater than minimal inference with usual sexual, social & functional activities. Vaginal discharge by participant report: Grade 1 (mild)-mild-moderate increase in amount above participant BL-no sanitary protection required; Grade 2 (moderate)-profuse increase in discharge requiring pad use or other hygienic intervention.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Irritation | Any vaginal itching | 2 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Irritation | Mild vaginal itching | 2 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Irritation | Moderate vaginal itching | 0 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Irritation | Any vaginal dryness | 1 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Irritation | Mild vaginal dryness | 0 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Irritation | Moderate vaginal dryness | 1 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Irritation | Any vaginal discharge | 3 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Irritation | Mild vaginal discharge | 3 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Irritation | Moderate vaginal discharge | 0 participants |
Secondary
Frequency and Intensity/Grade of Vaginal Pain
The frequency of participants with vaginal pain was presented in total and by categories of intensity/grade. The intensity of vaginal pain was evaluated as symptoms score of pain and dyspareunia (pain with sexual activity) as: Grade 1 (mild) - Pain causing no or minimal inference with usual social & functional activities; Grade 2 (moderate) - Pain causing greater than minimal inference with usual social & functional activities or the need for non-narcotic medication; Grade 3 (severe) - Pain causing inability to perform usual social & functional activities or the need for narcotic medication; Grade 4 (potentially life threatening) - Disabling pain causing inability to perform basic self-care functions OR hospitalization (other than emergency room visit) indicated. Dyspareunia (pain with sexual activity): Grade 1 (mild) - Pain causing no or minimal inference with sexual function; Grade 2 (moderate) - Pain causing greater than minimal inference with sexual function.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Pain | Any vaginal pain | 2 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Pain | Mild vaginal pain | 2 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Pain | Moderate vaginal pain | 1 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Pain | Severe vaginal pain | 0 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Pain | Potentially life threatening vaginal pain | 0 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Pain | Any dyspareunia | 1 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Pain | Mild dyspareunia | 0 participants |
| Progesterone Vaginal Ring | Frequency and Intensity/Grade of Vaginal Pain | Moderate dyspareunia | 1 participants |
Secondary
Frequency and Reason for PVR Discontinuation
Frequency of participants who prematurely discontinued PVR (i.e. did not fulfill 10 weeks of PVR treatment) was presented by reason.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Frequency and Reason for PVR Discontinuation | Withdrawal by participant | 2 participants |
| Progesterone Vaginal Ring | Frequency and Reason for PVR Discontinuation | Lost to follow-up | 1 participants |
| Progesterone Vaginal Ring | Frequency and Reason for PVR Discontinuation | Adverse event | 44 participants |
| Progesterone Vaginal Ring | Frequency and Reason for PVR Discontinuation | Personal issue | 1 participants |
Secondary
Frequency, Intensity/Grade, Seriousness, and Relatedness of Adverse Events (AEs)
The frequency of participants with total AEs, AEs by categories of intensity (mild, moderate, severe), seriousness and relatedness was presented. An AE is any untoward medical occurrence in a participant participating in a clinical trial. The intensity of an AE was classified using the following 3-point scale: mild=awareness of signs or symptoms, but no disruption of usual activity; moderate=event sufficient to affect usual activity (disturbing); or severe= inability to work or perform usual activities (unacceptable). Seriousness refers to death, hospitalization/ prolongation of existing hospitalization, a life-threatening experience, persistent or significant disability/incapacity, or congenital anomaly. The possibility of whether the IMP caused the AE would be classified as: reasonable possibility, no reasonable possibility. All the reasonable possible causality to the IMP were referred to as adverse drug reactions (ADRs). Relatedness of AEs to IMP was assessed by the investigator.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of Adverse Events (AEs) | Any AE | 124 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of Adverse Events (AEs) | Mild AE | 100 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of Adverse Events (AEs) | Moderate AE | 46 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of Adverse Events (AEs) | Severe AE | 9 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of Adverse Events (AEs) | Serious AE | 4 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of Adverse Events (AEs) | ADRs | 25 participants |
Secondary
Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal Adhesions
The frequency of participants with AEs associated with vaginal adhesion (total), by categories of intensity, seriousness, and relatedness was presented. The intensity was evaluated as symptoms score of vaginal adhesion as: Grade 0 (Normal) - None; Grade 1 (mild) - asymptomatic, manual removal of ring possible; Grade 2 (moderate) - Symptomatic (eg: irritation reported by participant), manual removal of ring possible; Grade 3 (severe) - Surgical intervention (eg: adhesiolysis) required to resolve; Grade 4 (potentially life threatening) - urgent intervention indicated. The AEs associated with vaginal adhesion of Grade 4 intensity were considered to be serious. Relatedness to IMP was assessed by investigator.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal Adhesions | 0 Participants |
Secondary
Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions
Frequency of participants with AEs associated with vaginal and cervical abrasions and lesions, by intensity, seriousness, & relatedness was presented. Intensity was evaluated as symptoms score: Vaginal/cervical lesions:Grade 0 (Normal)- Normal variants including skin tags, moles, scars, etc; Grade 1 (mild) - Blisters, ulcerations, or pustules, no treatment indicated; Grade 2 (moderate)- Blisters, ulcerations, or pustules with treatment indicated; Grade 3 (severe) - Severe epithelial disruption requiring hospitalization; Vaginal/cervical abrasions: Grade 0 (Normal) - None; Grade 1 (mild)- Superficial disruptions and disruptions extending through the mucosa with minimal impact on life; Grade 2 (moderate)- Large disruptions extending through the mucosa or large superficial disruptions, hospitalization not indicated; Grade 3 (severe)- Large disruptions extending through the mucosa or large superficial disruptions, hospitalization indicated. Relatedness to IMP was assessed by investigator.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions | Any Vaginal lesions | 1 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions | Mild vaginal lesion | 1 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions | Moderate vaginal lesion | 0 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions | Severe vaginal lesion | 0 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions | Serious vaginal lesion | 0 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions | Related vaginal lesion | 0 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions | Any vaginal abrasion | 0 participants |
| Progesterone Vaginal Ring | Frequency, Intensity/Grade, Seriousness, and Relatedness of AEs Associated With Vaginal and Cervical Abrasions and Lesions | Any cervical lesion | 0 participants |
Secondary
Positive β-hCG Rate at 2 Weeks and 2 Weeks +3-4 Days Post Oocyte Retrieval
Frequency of participants with positive β-hCG rate at 2 weeks and 2 weeks +3-4 Days was presented. Positive β-hCG was defined as a positive serum β-hCG test at 2 weeks and 2 weeks +3-4 Days post-oocyte retrieval.
Time frame: At 2 weeks and 2 weeks +3-4 Days post oocyte retrieval
Population: The mITT analysis set consisted of all participants who had successful oocyte retrieval, received at least 1 dose of IMP, and had completed fresh embryo transfer.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Progesterone Vaginal Ring | Positive β-hCG Rate at 2 Weeks and 2 Weeks +3-4 Days Post Oocyte Retrieval | 60.9 percentage of participants |
Secondary
Rate of Abnormal Findings in Clinical Laboratory Tests (Clinical Chemistry, Hematology, and Urinalysis)
Participants with at least one abnormal finding in clinical laboratory tests (i.e. abnormal clinical significant \[CS\] values: as assessed by investigator) were reported. Clinical chemistry included: glucose, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, potassium, sodium, chloride, calcium, estimated glomerular filtration rate, and gamma-glutamyl transferase; hematology included: basophils, eosinophils, hematocrit, hemoglobin, lymphocytes, monocytes, neutrophils, platelets, erythrocytes, and leukocytes; urinalysis included: specific gravity, ketones, pH, protein, blood, and glucose.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Rate of Abnormal Findings in Clinical Laboratory Tests (Clinical Chemistry, Hematology, and Urinalysis) | Potassium (mmol/L)<3.5->5.3 | 1 participants |
| Progesterone Vaginal Ring | Rate of Abnormal Findings in Clinical Laboratory Tests (Clinical Chemistry, Hematology, and Urinalysis) | Blood, traces | 1 participants |
Secondary
Rate of Abnormal Findings in Vital Signs
Participants with at least one abnormal finding (i.e. abnormal CS values: as assessed by investigator) in vital signs were reported. Vital signs includes: Weight (kg): decrease of \>=7% from baseline (BL) or increase of \>=7% from BL; Systolic Blood Pressure (SBP): \<=90 mmHg and decrease of \>=20 mmHg from BL or \>=180 mmHg and increase of \>= 20 mmHg from BL; Diastolic Blood Pressure (DBP): \<= 50 mmHg and decrease of \>= 15 mmHg from BL or \>=105 mmHg and increase of \>=15 mmHg from BL; Heart Rate: \<=50 (beats per minute \[bpm\]) and decrease of \>= 15 bpm from BL or \>=120 bpm and increase of \>=15 from BL; Temperature \>= 38.3 degree Celsius.
Time frame: From Day 1 of PVR treatment (day after oocyte retrieval) up to end-of-trial (12 weeks post-oocyte retrieval)
Population: The safety analysis set comprised of all participants treated with IMP.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Rate of Abnormal Findings in Vital Signs | Weight (kg), decrease of >=7% from BL | 4 participants |
| Progesterone Vaginal Ring | Rate of Abnormal Findings in Vital Signs | Weight (kg), increase of >=7% from BL | 23 participants |
| Progesterone Vaginal Ring | Rate of Abnormal Findings in Vital Signs | SBP (mmHg), <=90 and decrease >=20 from BL | 2 participants |
| Progesterone Vaginal Ring | Rate of Abnormal Findings in Vital Signs | DBP (mmHg), <=50 and decrease of>=15 from BL | 3 participants |
| Progesterone Vaginal Ring | Rate of Abnormal Findings in Vital Signs | DBP(mmHg),>=105 and increase of>=15 from BL | 1 participants |
| Progesterone Vaginal Ring | Rate of Abnormal Findings in Vital Signs | Heart Rate(bpm) <=50 and decrease of>= 15 from BL | 1 participants |
| Progesterone Vaginal Ring | Rate of Abnormal Findings in Vital Signs | Heart Rate(bpm) >=120 and increase of>= 15 from BL | 1 participants |
Secondary
Rate of Ectopic and Heterotopic Pregnancies Following Oocyte Retrieval
Frequency of participants with ectopic and heterotopic pregnancies was presented.
Time frame: At 4 weeks +3-4 Days after oocyte retrieval
Population: The mITT analysis set consisted of all participants who had successful oocyte retrieval, received at least 1 dose of IMP, and had completed fresh embryo transfer.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Progesterone Vaginal Ring | Rate of Ectopic and Heterotopic Pregnancies Following Oocyte Retrieval | Ectopic pregnancy | 0.4 percentage of participants |
| Progesterone Vaginal Ring | Rate of Ectopic and Heterotopic Pregnancies Following Oocyte Retrieval | Heterotopic pregnancy | 0.0 percentage of participants |