UMIN-ICDS Clinical Trial

Public title

A Comparative Study of the Efficacy and Safety of Follitropin Delta With Follitropin Alfa with Progestin Primed Ovarian Stimulation (PPOS) in Japanese Women Undergoing Assisted Reproductive Technology (ART)

Acronym

Comparative study of efficacy of follitropin delta and follitropin alfa on PPOS

Scientific Title

Non-inferiority Study of Follitropin Delta and Follitropin Alpha in Combined Progestin Primed Ovarian Stimulation (PPOS) in Japanese Women Undergoing Assisted Reproductive Technology (ART)

Scientific Title:Acronym

Non-inferiority study of follitropin delta and follitropin alfa to PPOS

Region

Japan

Condition

Primary and secondary infertility

Classification by specialty

Obstetrics and Gynecology

Classification by malignancy

Others

Genomic information

NO

Narrative objectives1

To evaluate whether the use of follitropin delta for progestin-primed ovarian stimulation (PPOS) has similar clinical outcomes as follitropin alfa.

Basic objectives2

Safety,Efficacy

Basic objectives -Others

Trial characteristics_1

Trial characteristics_2

Developmental phase

Primary outcomes

Percentage of good embryos available for embryo transfer

Key secondary outcomes

1.Proportion of Subjects With Extreme Ovarian Responses
Extreme ovarian response defined as <2, >25 oocytes retrieved. Subjects with cycle cancellation due to poor ovarian response are included as <1 oocytes retrieved.
2.Number of growing Follicles At oocyte retrieval
3. Number of picked up Follicles At oocyte retrieval
4. Percentage of Metaphase2 (M2) Oocytes
5.Fertilization Rate,The fertilization rate was defined as the number of oocytes with 2 pronuclei divided by the number of oocytes retrieved.
6.Number of premature Luteinizing Hormone (LH) surge occurrences
7.Proportion of Subjects With Early Ovarian hyper stimulation syndrome (OHSS) (Including OHSS of Moderate/Severe Grade) and/or Preventive Interventions for Early OHSS (Time Frame: Up to 9 days after triggering of final follicular maturation )
Early OHSS is defined as OHSS with onset <9 days after triggering of final follicular maturation. Classification of grade is according to Golan's classification system, and all OHSS cases are graded as mild, moderate or severe.
8.Circulating Concentrations of Estradiol, Progesterone, LH,FSH
9. Number of Stimulation Days
10.Number of Subjects With Adverse Events
11.Positive Beta Unit of Human Chorionic Gonadotropin (hCG) Rate
Defined as positive hCG test 13-15 days after embryo transfer.
12.Clinical Pregnancy Rate,Defined as at least one gestational sac 5-6 weeks after transfer.
13.Ongoing Pregnancy Rate,Defined as at least one intrauterine viable fetus 10-11 weeks after transfer.
14.Proportion of Subjects With Early Pregnancy Losses
Grouped according to occurrence of biochemical pregnancy, spontaneous abortion, vanishing twin or ectopic pregnancy (with and without medical/surgical intervention).
Frequency of early pregnancy losses are presented.

Study type

Interventional

Basic design

Parallel

Randomization

Non-randomized

Randomization unit

Blinding

Open -no one is blinded

Control

Active

Stratification

Dynamic allocation

Institution consideration

Blocking

Concealment

No. of arms

2

Purpose of intervention

Treatment

Type of intervention

Medicine

Interventions/Control_1

In the follitropin delta group (Study group), the initial dose is determined using an algorithm calculated from AMH and patient weight, and subcutaneous injection of follitropin delta is started on days 2-3 of the menstrual cycle. When performing ovarian stimulation, clomiphene or letrozole should also be taken from the beginning of the induction. Ovarian stimulation is performed with an oral progestin (dydrogesterone 10 mg/day or medroxyprogesterone acetate 5 mg/day) starting the day after the start of injections. The dosage of follitropin delta should not be changed during ovarian stimulation. Follicular monitoring started on day 8 or 9 of the menstrual cycle. This monitoring was performed every 2 to 4 days using a transvaginal ultrasound examination to check the growing follicular size and the number of follicles. When multiple follicles larger than 18 mm are observed, a GnRH agonist and HCG should be administered, and egg retrieval should be performed 36 hours later. After egg retrieval, fertilization is performed, the embryos are cultured to blastocysts, and good embryos are cryopreserved and transferred after menstruation begins.

Interventions/Control_2

In the follitropin alfa group (Control group), the initial dose was determined in 12.5 IU increments from 75 IU to 250 IU based on the AMH, the number of antral follicles at the start of ovarian stimulation, and age at the discretion of the physician, and the dose was not changed for the first 5 days, and subcutaneous injection was started on the second and third days of menstruation.Concomitant use of clomiphene and letrozole oral drugs and concomitant use of oral progestin preparations were also performed in the same way as in the study group. Follicular monitoring started on day 8 or 9 of the menstrual cycle. This monitoring was performed every 2 to 4 days using a transvaginal ultrasound examination to check the growing follicular size and the number of follicles. If follicular growth is slow, the dose of follitropin alfa can be increased during ovarian stimulation. When multiple follicles larger than 18 mm are observed, a GnRH agonist and HCG should be administered, and egg retrieval should be performed 36 hours later. After egg retrieval, fertilization is performed, the embryos are cultured to blastocysts, and good embryos are cryopreserved and transferred after menstruation begins.

Interventions/Control_3

Interventions/Control_4

Interventions/Control_5

Interventions/Control_6

Interventions/Control_7

Interventions/Control_8

Interventions/Control_9

Interventions/Control_10

Age-lower limit

20

years-old

<=

Age-upper limit

40

years-old

>=

Gender

Female

Key inclusion criteria

1. Written informed consent is obtained from the patients who are enrolled.
2.Age younger than 41 years, willing to undergo assisted reproductive treatment at our clinic
3.Anti-Mullerian hormone (AMH) levels greater than 1.0 ng/ml
4. First or second time of IVF/intra-cytoplasmic sperm injection (ICSI) at our clinic
5.Regular menstrual cycles of 24-35 days (both inclusive), presumed to be ovulatory.
6.In good physical and mental health in the judgement of the investigator.
7.Body mass index (BMI) between 17.5 and 32.0 kg/m2 (both inclusive) at screening.

Key exclusion criteria

Known endometriosis stage III-IV (defined by the revised ASRM classification, 1996).
One or more follicles >10 mm (including cysts) observed on the transvaginal ultrasound prior to randomization on stimulation day 1 (puncture of cysts is allowed prior to randomization)
Patients with untreated hydrosalpinx
Patients with untreated intrauterine lesions (endometrial polyps or submucosal myoma)
Patients with serious primary disease
Patients with uncontrolled diabetes or other endocrine complications

Target sample size

500

Name of lead principal investigator

1st name	Hirobumi
Middle name
Last name	Kamiya

Organization

Kamiya Ladies Clinic

Division name

Reproductive health

Zip code

0600003

Address

Nittsu Sapporo Bldg 2F, 2-1, Nishi2, Kita3, Chuo-ku, Sapporo, Hokkaido, 0600003, Japan

TEL

+81-11-231-2722

Email

kamiya@fine.ocn.ne.jp

Name of contact person

1st name	Nanako
Middle name
Last name	Iwami

Organization

Kamiya Ladies Clinic

Division name

Reproductive health

Zip code

0600003

Address

Nittsu Sapporo Bldg 2F, 2-1, Nishi2, Kita3, Chuo-ku, Sapporo, Hokkaido, 0600003, Japan

TEL

+81-231-2722

Homepage URL

Email

iwami@kamiyaclinic.com

Institute

Kamiya Ladies Clinic

Institute

Department

Personal name

Organization

Kamiya Ladies Clinic

Organization

Division

Category of Funding Organization

Self funding

Nationality of Funding Organization

Co-sponsor

Name of secondary funder(s)

Organization

Kamiya Ladies Clinic

Address

Nittsu Sapporo Bldg 2F, 2-1, Nishi2, Kita3, Chuo-ku, Sapporo, Hokkaido, 0600003, Japan

Tel

+81-11-231-2722

Email

tozawa@kamiyaclinic.com

Secondary IDs

NO

Study ID_1

Org. issuing International ID_1

Study ID_2

Org. issuing International ID_2

IND to MHLW

Institutions

Date of disclosure of the study information

2023

Year

01

Month

10

Day

URL releasing protocol

Publication of results

Unpublished

URL related to results and publications

Number of participants that the trial has enrolled

Results

Results date posted

Results Delayed

Results Delay Reason

Date of the first journal publication of results

Baseline Characteristics

Participant flow

Adverse events

Outcome measures

Plan to share IPD

IPD sharing Plan description

Recruitment status

Open public recruiting

Date of protocol fixation

2022

Year

12

Month

23

Day

Date of IRB

2022

Year

12

Month

24

Day

Anticipated trial start date

2023

Year

01

Month

10

Day

Last follow-up date

2025

Year

01

Month

09

Day

Date of closure to data entry

Date trial data considered complete

Date analysis concluded

Other related information

Registered date

2023

Year

01

Month

08

Day

Last modified on

2024

Year

02

Month

28

Day

Link to view the page

Value
https://center6.umin.ac.jp/cgi-open-bin/icdr_e/ctr_view.cgi?recptno=R000056919